Toxins

2024

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17 pages, 7834 KiB

Open AccessArticle

Protective Effects of Astaxanthin on Ochratoxin A-Induced Liver Injury: Effects of Endoplasmic Reticulum Stress and Mitochondrial Fission–Fusion Balance

by Yiting Zou, Shiyi Zhang, Jian Yang, Chen Qin, Bo Jin, Zhenyu Liang, Shuhua Yang, Lin Li and Miao Long

Toxins 2024, 16(2), 68; https://doi.org/10.3390/toxins16020068 - 30 Jan 2024

Cited by 1 | Viewed by 2004

Abstract

Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects [...] Read more.

Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects of ASTA on the OTA-induced damage of the endoplasmic reticulum and mitochondria in broiler liver samples by serum biochemical analysis, antioxidant analysis, qRT-PCR, and Western blot analysis. ASTA inhibited the expressions of ahr, pxr, car, cyp1a1, cyp1a5, cyp2c18, cyp2d6, and cyp3a9 genes, and significantly alleviated OTA-induced liver oxidative damage (SOD, GSH-Px, GSH, MDA). Furthermore, it inhibited OTA-activated endoplasmic reticulum stress genes and proteins (grp94, GRP78, atf4, ATF6, perk, eif2α, ire1, CHOP). ASTA alleviated OTA-induced mitochondrial dynamic imbalance, inhibited mitochondrial division (DRP1, mff), and promoted mitochondrial fusion (OPA1, MFN1, MFN2). In conclusion, ASTA can decrease OTA-induced oxidative damage, thereby alleviating endoplasmic reticulum stress and mitochondrial dynamic imbalance. Full article

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2022

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10 pages, 610 KiB

Open AccessArticle

Comparative Evaluation of the Capacity of Commercial and Autochthonous Saccharomyces cerevisiae Strains to Remove Ochratoxin A from Natural and Synthetic Grape Juices

by Islem Dammak, Norah Salem Alsaiari, Imene Fhoula, Abdelfattah Amari, Zohra Hamdi, Mnasser Hassouna, Faouzi Ben Rebah, Tahar Mechichi and Salma Lasram

Toxins 2022, 14(7), 465; https://doi.org/10.3390/toxins14070465 - 7 Jul 2022

Cited by 3 | Viewed by 1894

Abstract

In this paper, we assessed the ability of two strains of Saccharomyces cerevisiae, in viable and dead forms, to remove ochratoxin A (OTA) from an artificially contaminated synthetic grape juice medium (SGM) (10 µg OTA/L) and a naturally contaminated grape juice (6.64 [...] Read more.

In this paper, we assessed the ability of two strains of Saccharomyces cerevisiae, in viable and dead forms, to remove ochratoxin A (OTA) from an artificially contaminated synthetic grape juice medium (SGM) (10 µg OTA/L) and a naturally contaminated grape juice (6.64 µg OTA/L). The first strain, named Levulin FB, is a commercial yeast used in making wine. The second, named SC5, is an autochthonous strain isolated from table grapes. OTA concentrations in juices before and after their contact with yeast cells were assessed. A significant decrease in OTA level (p < 0.05) in the SGM medium and in the natural grape juice was observed after 1 h of adding yeast cells (20 g/L) in viable and heat-treated forms. It was inferred that the dead forms of the two strains were more able to eliminate OTA than their viable forms in both media. This study demonstrates the potential application of an autochthonous yeast for the natural decontamination of grape juice from fungal toxins. Full article

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2021

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17 pages, 2272 KiB

Open AccessArticle

Efflux at the Blood-Brain Barrier Reduces the Cerebral Exposure to Ochratoxin A, Ochratoxin α, Citrinin and Dihydrocitrinone

by Matthias Behrens, Sabine Hüwel, Hans-Joachim Galla and Hans-Ulrich Humpf

Toxins 2021, 13(5), 327; https://doi.org/10.3390/toxins13050327 - 30 Apr 2021

Cited by 12 | Viewed by 3111

Abstract

Recent studies have implied that environmental toxins, such as mycotoxins, are risk factors for neurodegenerative diseases. To act directly as neurotoxins, mycotoxins need to penetrate or affect the integrity of the blood-brain barrier, which protects the mammalian brain from potentially harmful substances. As [...] Read more.

Recent studies have implied that environmental toxins, such as mycotoxins, are risk factors for neurodegenerative diseases. To act directly as neurotoxins, mycotoxins need to penetrate or affect the integrity of the blood-brain barrier, which protects the mammalian brain from potentially harmful substances. As common food and feed contaminants of fungal origin, the interest in the potential neurotoxicity of ochratoxin A, citrinin and their metabolites has recently increased. Primary porcine brain capillary endothelial cells were used to investigate cytotoxic or barrier-weakening effects of ochratoxin A, ochratoxin α, citrinin and dihydrocitrinone. The transfer and transport properties of the mycotoxins across the barrier formed by porcine brain capillary endothelial cell monolayers were analysed using HPLC-MS/MS. High levels of Ochratoxin A caused cytotoxic and barrier-weakening effects, whereas ochratoxin α, citrinin and dihydrocitrinone showed no adverse effects up to 10 µM. Likely due to efflux transporter proteins, the transfer to the brain compartment was much slower than expected from their high lipophilicity. Due to their slow transfer across the blood-brain barrier, cerebral exposure of ochratoxin A, ochratoxin α, citrinin and dihydrocitrinone is low and neurotoxicity is likely to play a subordinate role in their toxicity at common physiological concentrations. Full article

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16 pages, 2962 KiB

Open AccessArticle

Quantitative Proteomic Profiling of Fungal Growth, Development, and Ochratoxin A Production in Aspergillus ochraceus on High- and Low-NaCl Cultures

by Yan Wang, Yue Guan, Wei Lin, Hao Yan, Jing Neng and Peilong Sun

Toxins 2021, 13(1), 51; https://doi.org/10.3390/toxins13010051 - 13 Jan 2021

Cited by 8 | Viewed by 2592

Abstract

Dry-cured meat products are worldwide food with high-salt content, and filamentous fungi are beneficial to the maturation process. However, some salt-tolerant strains of Aspergillus and Penicillium produce ochratoxin A (OTA) on these products and thus threaten food safety. In our study, proteomic analysis [...] Read more.

Dry-cured meat products are worldwide food with high-salt content, and filamentous fungi are beneficial to the maturation process. However, some salt-tolerant strains of Aspergillus and Penicillium produce ochratoxin A (OTA) on these products and thus threaten food safety. In our study, proteomic analysis was performed to reveal the mechanism of adaptability to high-salt environment by Aspergillus ochraceus. Twenty g/L and 70 g/L NaCl substrates were used to provide medium- and high-NaCl content environments, respectively. The NaCl addition could induce fungal growth, but only 20 g/L NaCl addition could induce spore production while 70 g/L repressed it. Proteomics analysis identified 2646 proteins in A. ochraceus fc-1, of which 237 and 251 were differentially expressed with 20 g/L and 70 g/L NaCl addition, respectively. Potential factors affecting fungal growth and development were identified by GO and KEGG analyses of biological process, cellular component, and molecular function terms. The results revealed that ergosterol synthesis pathway was significantly upregulated with 20 g/L and 70 g/L NaCl addition. However, fungal growth and development including OTA production were complex processes associated with many factors including nutrient uptake, cell membrane integrity, cell cycle, energy metabolism, intracellular redox homeostasis, protein synthesis and processing, autophagy, and secondary metabolism. Reactive oxygen species may be an important window to understand the mechanism that medium-salt content was conducive to intracellular signal transduction while high-salt content caused oxidative stress. The findings would help to improve the processes and storage conditions of dry-cured meat products. Full article

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2020

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15 pages, 3004 KiB

Open AccessArticle

The Influence of NaCl and Glucose Content on Growth and Ochratoxin A Production by Aspergillus ochraceus, Aspergillus carbonarius and Penicillium nordicum

by Yan Wang, Hao Yan, Jing Neng, Jian Gao, Bolei Yang and Yang Liu

Toxins 2020, 12(8), 515; https://doi.org/10.3390/toxins12080515 - 12 Aug 2020

Cited by 20 | Viewed by 3860

Abstract

Ochratoxin A (OTA) is a nephrotoxic mycotoxin, which deserves particular attention for its widespread contamination of a variety of food and feed. Aspergillus ochraceus, Aspergillus carbonarius, and Penicillium nordicum are an important source of OTA in three different kinds of food [...] Read more.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin, which deserves particular attention for its widespread contamination of a variety of food and feed. Aspergillus ochraceus, Aspergillus carbonarius, and Penicillium nordicum are an important source of OTA in three different kinds of food commodities, including cereals, grape and dried fruit products, and dry-cured meat products. Deeper knowledge of OTA production and mycelium growth related to the high-sugar or NaCl-rich environments was gained in this manuscript. A. ochraceus and P. nordicum were likely to have greater growth rates in medium supplied with certain concentrations of NaCl (0–80 g/L), and the colony diameter was the largest at the salt content of 40 g/L. P. nordicum was more suitable to grow in NaCl-riched medium, the OTA production was increased to 316 ppb from 77 ppb when 20 g/L NaCl was added. The capability of OTA production was inhibited when salt content was 40 g/L and 60 g/L in A. ochraceus and P. nordicum, respectively. As the glucose content increased to 250 g/L, the capacity of mycelium growth and sporulation was increased significantly in A. ochraceus and A. carbonarius. A. carbonarius was more suitable to grow in high-sugar grape products. OTA production was significantly promoted with an added 100 g/L glucose in A. carbonarius. OTA production was inhibited when glucose content was 150 g/L and in 200 g/L in A. ochraceus and A. carbonarius, respectively. NaCl and glucose have an effect on fungal growth and OTA production, and the activation of biosynthetic genes of OtaA. These results would allow designing new strategies to prevent OTA accumulation on sugar or NaCl-riched foodstuffs and achieve the objective to manufacture cereals, dried vine fruits and dry-cured ham, free of OTA. Full article

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2018

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16 pages, 5030 KiB

Open AccessArticle

Interaction of 2′R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells

by Zelma Faisal, Diána Derdák, Beáta Lemli, Sándor Kunsági-Máté, Mónika Bálint, Csaba Hetényi, Rita Csepregi, Tamás Kőszegi, Franziska Sueck, Benedikt Cramer, Hans-Ulrich Humpf and Miklós Poór

Toxins 2018, 10(9), 353; https://doi.org/10.3390/toxins10090353 - 1 Sep 2018

Cited by 11 | Viewed by 4454

Abstract

Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-OTA (and OTA) with high affinity; therefore, albumin may influence the [...] Read more.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-OTA (and OTA) with high affinity; therefore, albumin may influence the tissue uptake and elimination of ochratoxins. We aimed to investigate the binding site of 2′R-OTA (verses OTA) in HSA and the displacing effects of site markers to explore which molecules can interfere with its albumin-binding. Affinity of 2′R-OTA toward albumins from various species (human, bovine, porcine and rat) was tested to evaluate the interspecies differences regarding 2′R-OTA-albumin interaction. Thermodynamic studies were performed to give a deeper insight into the molecular background of the complex formation. Besides fluorescence spectroscopic and modeling studies, effects of HSA, and fetal bovine serum on the cytotoxicity of 2′R-OTA and OTA were tested in MDCK kidney cell line in order to demonstrate the influence of albumin-binding on the cellular uptake of ochratoxins. Site markers displaced more effectively 2′R-OTA than OTA from HSA. Fluorescence and binding constants of 2′R-OTA-albumin and OTA-albumin complexes showed different tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2′R-OTA, even at sub-toxic concentrations, increased the toxic action of OTA. Full article

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9 pages, 1399 KiB

Open AccessArticle

Low Doses of Ochratoxin-A Decrease IgY and IgA Production in Broiler Chicks

by Shahzad A. Khan, Emerson J. Venancio, Eduardo V. Fernandes, Elisa Y. Hirooka, Alexandre Oba, Karina K. M. C. Flaiban and Eiko N. Itano

Toxins 2018, 10(8), 316; https://doi.org/10.3390/toxins10080316 - 6 Aug 2018

Cited by 13 | Viewed by 4678

Abstract

The mycotoxin, ochratoxin-A (OTA), produced by some fungi, and is a natural contaminant of many foods and animal feeds worldwide. Due to its toxic effects, the recommended maximum daily intake of OTA for poultry feeds is 0.1 mg OTA/kg (ECR2006/575/EC); this dose does [...] Read more.

The mycotoxin, ochratoxin-A (OTA), produced by some fungi, and is a natural contaminant of many foods and animal feeds worldwide. Due to its toxic effects, the recommended maximum daily intake of OTA for poultry feeds is 0.1 mg OTA/kg (ECR2006/575/EC); this dose does not induce changes in hepatic/renal parameters, but decreases thymus size and serum globulin concentrations. Accordingly, in this study, we assessed quantitatively the total circulating IgY and IgA serum levels, in chicks consuming a 0.1 mg OTA/kg diet (limit) and higher doses (0.3–1.1 mg OTA/kg diet) for 14 or 21 days. We also evaluated other immunological parameters (thymus, bursa of Fabricius, and spleen weights and leukocyte profiles) at day 21. Decreased IgY serum levels were observed in all OTA-treated groups (p < 0.05). In the low-dose group, IgA levels were decreased on day 21, but not on day 14. The size of the thymus and the bursa of Fabricius was decreased in all OTA-treated groups (p < 0.05), whereas reduced spleen size and altered leukocyte profiles were detected only in the high-dose group (p < 0.05). We concluded that chronic exposure to OTA, even at the recommended highest dose, affected IgY and IgA production in chicks. Full article

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14 pages, 1312 KiB

Open AccessArticle

Toxicity of Ochratoxin to Early Life Stages of Zebrafish (Danio rerio)

by Linda Tschirren, Seraina Siebenmann and Constanze Pietsch

Toxins 2018, 10(7), 264; https://doi.org/10.3390/toxins10070264 - 28 Jun 2018

Cited by 21 | Viewed by 4462

Abstract

Ochratoxin A (OTA) is a known contaminant in fish feed but its effect on fish health remains rather unknown. A study was conducted to investigate the effects of different concentrations of ochratoxin on early life stages of zebrafish (Danio rerio). The [...] Read more.

Ochratoxin A (OTA) is a known contaminant in fish feed but its effect on fish health remains rather unknown. A study was conducted to investigate the effects of different concentrations of ochratoxin on early life stages of zebrafish (Danio rerio). The tests with ochratoxin A showed a correlation between the exposure to mycotoxin and the amount of damage. The mortality rate and the incidents of embryonal damage was increased by increasing ochratoxin concentrations. The calculations resulted in a lethal concentration for 50% of the embryos (LC₅₀) of 0.29 mg/L and a concentration at which 50% of the animals showed impairment (EC₅₀) of 0.36 mg/L after 96 h of exposure. During the test, reduced heart rates were also observed revealing a clear dose-response relationship. The EC₅₀ determination for this endpoint was 1.26 mg/L after 72 h of exposure. The measurement of oxidative stress was proven to be the most sensitive system to indicate OTA effects on the zebrafish embryos with an EC₅₀ value of 0.067 mg/L after 72 h of exposure. The test validity was given because the control test with 3,4-Dichloroaniline (3,4-D) showed a LC₅₀ value of 2.88 mg after 96 h of exposure which is comparable to the available reference values. According to the current knowledge, these experimental doses did not exceed the environmental concentrations of this ochratoxin A. However, this study raises concerns about the effects of ochratoxin on fish. Full article

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17 pages, 7581 KiB

Open AccessArticle

Interaction of Ochratoxin A and Its Thermal Degradation Product 2′R-Ochratoxin A with Human Serum Albumin

by Franziska Sueck, Miklós Poór, Zelma Faisal, Christoph G. W. Gertzen, Benedikt Cramer, Beáta Lemli, Sándor Kunsági-Máté, Holger Gohlke and Hans-Ulrich Humpf

Toxins 2018, 10(7), 256; https://doi.org/10.3390/toxins10070256 - 22 Jun 2018

Cited by 30 | Viewed by 4980

Abstract

Ochratoxin A (OTA) is a toxic secondary metabolite produced by several fungal species of the genus Penicillium and Aspergillus. 2′R-Ochratoxin A (2′R-OTA) is a thermal isomerization product of OTA formed during food processing at high temperatures. Both compounds [...] Read more.

Ochratoxin A (OTA) is a toxic secondary metabolite produced by several fungal species of the genus Penicillium and Aspergillus. 2′R-Ochratoxin A (2′R-OTA) is a thermal isomerization product of OTA formed during food processing at high temperatures. Both compounds are detectable in human blood in concentrations between 0.02 and 0.41 µg/L with 2′R-OTA being only detectable in the blood of coffee drinkers. Humans have approximately a fifty-fold higher exposure through food consumption to OTA than to 2′R-OTA. In human blood, however, the differences between the concentrations of the two compounds is, on average, only a factor of two. To understand these unexpectedly high 2′R-OTA concentrations found in human blood, the affinity of this compound to the most abundant protein in human blood the human serum albumin (HSA) was studied and compared to that of OTA, which has a well-known high binding affinity. Using fluorescence spectroscopy, equilibrium dialysis, circular dichroism (CD), high performance affinity chromatography (HPAC), and molecular modelling experiments, the affinities of OTA and 2′R-OTA to HSA were determined and compared with each other. For the affinity of HSA towards OTA, a logK of 7.0–7.6 was calculated, while for its thermally produced isomer 2′R-OTA, a lower, but still high, logK of 6.2–6.4 was determined. The data of all experiments showed consistently that OTA has a higher affinity to HSA than 2′R-OTA. Thus, differences in the affinity to HSA cannot explain the relatively high levels of 2′R-OTA found in human blood samples. Full article

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16 pages, 13747 KiB

Open AccessArticle

OTA Prevention and Detoxification by Actinobacterial Strains and Activated Carbon Fibers: Preliminary Results

by Rhoda El Khoury, Elodie Choque, Anthony El Khoury, Selma P. Snini, Robbie Cairns, Caroline Andriantsiferana and Florence Mathieu

Toxins 2018, 10(4), 137; https://doi.org/10.3390/toxins10040137 - 24 Mar 2018

Cited by 12 | Viewed by 5989

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium that contaminate food and feed raw materials. To reduce OTA contamination, we first tested in vitro, actinobacterial strains as potential biocontrol agents and afterward, through a physical decontamination method [...] Read more.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium that contaminate food and feed raw materials. To reduce OTA contamination, we first tested in vitro, actinobacterial strains as potential biocontrol agents and afterward, through a physical decontamination method using activated carbon fibers (ACFs). Actinobacterial strains were screened for their ability to reduce OTA in solid co-culture with A. carbonarius, which is the major OTA-producing species in European vineyards. Four strains showed a high affinity for removing OTA (67%–83%) with no significant effect on fungal growth (<20%). The mechanism of action was first studied by analyzing the expression of OTA cluster genes (acOTApks, acOTAnrps, acOTAhal) by RT-qPCR showing a drastic reduction in all genes (7–15 times). Second, the ability of these strains to degrade OTA was assessed in vitro on ISP2 solid medium supplemented with OTA (100 µg/L). Two strains reduced OTA to undetectable levels. As for the physical method, high adsorption rates were obtained for ACFs at 0.8 g/L with a 50% adsorption of OTA in red wine by AC15 and 52% in grape juice by AC20 within 24 h. These promising methods could be complementarily applied toward reducing OTA contamination in food chains, which promotes food safety and quality. Full article

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17 pages, 4566 KiB

Open AccessArticle

Chemometric Analysis of the Volatile Compounds Generated by Aspergillus carbonarius Strains Isolated from Grapes and Dried Vine Fruits

by Zhan Cheng, Menghua Li, Philip J. Marriott, Xiaoxu Zhang, Shiping Wang, Jiangui Li and Liyan Ma

Toxins 2018, 10(2), 71; https://doi.org/10.3390/toxins10020071 - 6 Feb 2018

Cited by 18 | Viewed by 5596

Abstract

Ochratoxin A (OTA) contamination in grape production is an important problem worldwide. Microbial volatile organic compounds (MVOCs) have been demonstrated as useful tools to identify different toxigenic strains. In this study, Aspergillus carbonarius strains were classified into two groups, moderate toxigenic strains (MT) [...] Read more.

Ochratoxin A (OTA) contamination in grape production is an important problem worldwide. Microbial volatile organic compounds (MVOCs) have been demonstrated as useful tools to identify different toxigenic strains. In this study, Aspergillus carbonarius strains were classified into two groups, moderate toxigenic strains (MT) and high toxigenic strains (HT), according to OTA-forming ability. The MVOCs were analyzed by GC-MS and the data processing was based on untargeted profiling using XCMS Online software. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was performed using extract ion chromatogram GC-MS datasets. For contrast, quantitative analysis was also performed. Results demonstrated that the performance of the OPLS-DA model of untargeted profiling was better than the quantitative method. Potential markers were successfully discovered by variable importance on projection (VIP) and t-test. (E)-2-octen-1-ol, octanal, 1-octen-3-one, styrene, limonene, methyl-2-phenylacetate and 3 unknown compounds were selected as potential markers for the MT group. Cuparene, (Z)-thujopsene, methyl octanoate and 1 unknown compound were identified as potential markers for the HT groups. Finally, the selected markers were used to construct a supported vector machine classification (SVM-C) model to check classification ability. The models showed good performance with the accuracy of cross-validation and test prediction of 87.93% and 92.00%, respectively. Full article

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2017

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4002 KiB

Open AccessArticle

High Incidence and Levels of Ochratoxin A in Wines Sourced from the United States

by Christopher Lawrence De Jesus, Amanda Bartley, Aaron Z. Welch and John P. Berry

Toxins 2018, 10(1), 1; https://doi.org/10.3390/toxins10010001 - 21 Dec 2017

Cited by 30 | Viewed by 11129

Abstract

Ochratoxin A (OTA) is one of the most prevalent mycotoxin contaminants of food crops. Among the agricultural products consequently contaminated by OTA is wine. In the present study, a sample of wines sourced from the United States was assessed for OTA. Wines were [...] Read more.

Ochratoxin A (OTA) is one of the most prevalent mycotoxin contaminants of food crops. Among the agricultural products consequently contaminated by OTA is wine. In the present study, a sample of wines sourced from the United States was assessed for OTA. Wines were primarily analyzed by high-performance liquid chromatography with fluorescence detection (HPLC-FD) coupled to a liquid-liquid extraction (LLE) technique which was developed and validated as a simplified sample preparation approach. More than 85% of the wines evaluated were found to contain OTA, at levels above the limit-of-detection (LOD = 0.1 µg L⁻¹), and 76% were above the limit-of-quantitation (LOQ = 0.3 µg L⁻¹) for the LLE/HPLC-FD method. More than two-thirds of the wines above the LOQ were found to exceed 1 µg L⁻¹. Complementary analysis by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) confirmed OTA in 74% of the OTA-positive wines (i.e., >LOQ by HPLC-FD). Overall, both the occurrence and measured levels of OTA were generally high, specifically relative to previous assessments of OTA in wine, and two of the wines were above the only current (European Union) regulatory limit of two parts-per-billion (ppb, ~2 µg L⁻¹). Possible trends with respect to geographical region and/or growing climate are noted. As the first assessment of U.S. wines in more than a decade, the overall high occurrence and levels of OTA in wine, and possible geographic and climatic trends, point to a need for regular surveillance of wines, as well as investigation of the relevant contributors to OTA occurrence toward mitigating contamination and exposure risks. Full article

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Open AccessArticle

Immunohistochemical Analysis of Rat Renal Tumours Caused by Ochratoxin A

by Diana Herman and Peter Mantle

Toxins 2017, 9(12), 384; https://doi.org/10.3390/toxins9120384 - 28 Nov 2017

Cited by 14 | Viewed by 6391

Abstract

Experimental renal cancer caused by ochratoxin A (OTA) in rats was first defined in the US National Toxicology Program (1989) and raised questions about any aetiological role in human urinary tract tumours. A review of histopathology in several rat kidney tumours from dietary [...] Read more.

Experimental renal cancer caused by ochratoxin A (OTA) in rats was first defined in the US National Toxicology Program (1989) and raised questions about any aetiological role in human urinary tract tumours. A review of histopathology in several rat kidney tumours from dietary OTA in recently described London studies, augmented by clinical immunohistochemistry for the first time for this mycotoxin, establishes their renal tubular cell origin. It had been assumed that the toxin might cause the human urothelial tumours associated with Balkan endemic nephropathy, but the present study could not support this. Comparison with a similar review of a metastasising renal tumour from a female rat of the NTP study consistently shows the kidney as the primary carcinogenic site for OTA. Morphological heterogeneity of these kidney tumours as epithelioid and/or sarcomatoid is revealed. Leiomyosarcoma was also diagnosed, and rhabdomyosarcoma differentiation was observed in the exceptionally aggressive NTP female tumour. The present pilot study involving immunohistochemistry indicates need for wider review of archived tumours for experimental evidence before formulating any epidemiological basis from a rat model for OTA’s relevance to idiopathic human renal cell carcinoma. Although the NTP study concluded that females are less sensitive to OTA than males, some female tumours still had heterogeneous morphology. Full article

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Open AccessArticle

Differential Gene Expression Analysis of Bovine Macrophages after Exposure to the Penicillium Mycotoxins Citrinin and/or Ochratoxin A

by Kristen M. Brennan, Se-Young Oh, Alexandros Yiannikouris, Daniel E. Graugnard and Niel A. Karrow

Toxins 2017, 9(11), 366; https://doi.org/10.3390/toxins9110366 - 13 Nov 2017

Cited by 21 | Viewed by 5534

Abstract

Mycotoxins produced by fungal species commonly contaminate livestock feedstuffs, jeopardizing their health and diminishing production. Citrinin (CIT) and ochratoxin A (OTA) are mycotoxins produced by Penicillium spp. and commonly co-occur. Both CIT and OTA can modulate immune response by inhibiting cell proliferation and [...] Read more.

Mycotoxins produced by fungal species commonly contaminate livestock feedstuffs, jeopardizing their health and diminishing production. Citrinin (CIT) and ochratoxin A (OTA) are mycotoxins produced by Penicillium spp. and commonly co-occur. Both CIT and OTA can modulate immune response by inhibiting cell proliferation and differentiation, altering cell metabolism, and triggering programmed cell death. The objective of this study was to determine the effects of sublethal exposure (i.e., the concentration that inhibited cell proliferation by 25% (IC₂₅)) to CIT, OTA or CIT + OTA on the bovine macrophage transcriptome. Gene expression was determined using the Affymetrix Bovine Genome Array. After 6 h of exposure to CIT, OTA or CIT + OTA, the number of differentially expressed genes (DEG), respectively, was as follows: 1471 genes (822 up-regulated, 649 down-regulated), 5094 genes (2611 up-regulated, 2483 down-regulated) and 7624 genes (3984 up-regulated, 3640 down-regulated). Of these, 179 genes (88 up-regulated, 91 down-regulated) were commonly expressed between treatments. After 24 h of exposure to CIT, OTA or CIT + OTA the number of DEG, respectively, was as follows: 3230 genes (1631 up-regulated, 1599 down-regulated), 8558 genes (4167 up-regulated, 4391 down-regulated), and 10,927 genes (6284 up-regulated, 4643 down-regulated). Of these, 770 genes (247 up-regulated, 523 down-regulated) were commonly expressed between treatments. The categorization of common biological functions and pathway analysis suggests that the IC₂₅ of both CIT and OTA, or their combination, induces cellular oxidative stress, a slowing of cell cycle progression, and apoptosis. Collectively, these effects contribute to inhibiting bovine macrophage proliferation. Full article

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Open AccessArticle

iTRAQ Mitoproteome Analysis Reveals Mechanisms of Programmed Cell Death in Arabidopsis thaliana Induced by Ochratoxin A

by Yan Wang, Xiaoli Peng, Zhuojun Yang, Weiwei Zhao, Wentao Xu, Junran Hao, Weihong Wu, Xiao Li Shen, Yunbo Luo and Kunlun Huang

Toxins 2017, 9(5), 167; https://doi.org/10.3390/toxins9050167 - 18 May 2017

Cited by 26 | Viewed by 5404

Abstract

Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major [...] Read more.

Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major endogenous source is mitochondria. However, there has been no evidence as to whether OTA induces directly PCD in plants until now. In this study, the presence of OTA in Arabidopsis thaliana leaves triggered accelerated respiration, increased production of mitochondrial ROS, the opening of ROS-dependent mitochondrial permeability transition pores and a decrease in mitochondrial membrane potential as well as the release of cytochrome c into the cytosol. There were 42 and 43 significantly differentially expressed proteins identified in response to exposure to OTA for 8 and 24 h, respectively, according to iTRAQ analysis. These proteins were mainly involved in perturbation of the mitochondrial electron transport chain, interfering with ATP synthesis and inducing PCD. Digital gene expression data at transcriptional level was consistent with the cell death induced by OTA being PCD. These results indicated that mitochondrial dysfunction was a prerequisite for OTA-induced PCD and the initiation and execution of PCD via a mitochondrial-mediated pathway. Full article

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Open AccessArticle

Initial Spore Density Has an Influence on Ochratoxin A Content in Aspergillus ochraceus CGMCC 3.4412 in PDB and Its Interaction with Seeds

by Caiyan Li, Yanmin Song, Lu Xiong, Kunlun Huang and Zhihong Liang

Toxins 2017, 9(4), 146; https://doi.org/10.3390/toxins9040146 - 21 Apr 2017

Cited by 8 | Viewed by 5057

Abstract

The morphology and secondary metabolism of Aspergillus spp. are associated with initial spore density (ISD). Fatty acids (FA) are involved in the biosynthesis of aflatoxins (AF) through Aspergillus quorum sensing (QS). Here, we studied how ochratoxin A (OTA) was regulated by spore density [...] Read more.

The morphology and secondary metabolism of Aspergillus spp. are associated with initial spore density (ISD). Fatty acids (FA) are involved in the biosynthesis of aflatoxins (AF) through Aspergillus quorum sensing (QS). Here, we studied how ochratoxin A (OTA) was regulated by spore density in Aspergillus ochraceus CGMCC 3.4412. The results contribute to understanding the role of spore density in morphogenesis, OTA biosynthesis, and host–pathogen interactions. When A. ochraceus was grown in Potato Dextrose Broth (PDB) media at different spore densities (from 10¹ to 10⁶ spores/mL), more OTA was produced when ISD were increased, but a higher level of ISD inhibited OTA biosynthesis. Seed infection studies showed that peanuts (Arachis hypogaea) and soybeans (Glycine max) with high FA content were more susceptible to OTA production when infected by A. ochraceus and reactive oxygen species (ROS)-induced OTA biosynthesis. These results suggested that FA was vital for OTA biosynthesis, and that oxidative stress was closely related to OTA biosynthesis in A. ochraceus. Full article

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Open AccessReply

Reply to Comment on “Screening and Identification of Novel Ochratoxin A-Producing Fungi from Grapes”. Toxins 2016, 8, 333”–in Reporting Ochratoxin A Production from Strains of Aspergillus, Penicillium and Talaromyces

by Xiaoyun Zhang, Yulin Li, Haiying Wang, Xiangyu Gu, Xiangfeng Zheng, Yun Wang, Junwei Diao, Yaping Peng and Hongyin Zhang

Toxins 2017, 9(2), 66; https://doi.org/10.3390/toxins9020066 - 14 Feb 2017

Cited by 3 | Viewed by 4318

Abstract

We sincerely thank you and Dr. Giancarlo Perrone, Antonio F. Logrieco and Jens C. Frisvda for the suggestions and concerns raised with regard to our paper entitled “Screening and Identification of Novel ochratoxin A-Producing Fungi from Grapes” which was published in Toxins.[...] Full article

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Open AccessComment

Comments on “Screening and Identification of Novel Ochratoxin A-Producing Fungi from Grapes. Toxins 2016, 8, 333”—In Reporting Ochratoxin A Production from Strains of Aspergillus, Penicillium and Talaromyces

by Giancarlo Perrone, Antonio F. Logrieco and Jens C. Frisvad

Toxins 2017, 9(2), 65; https://doi.org/10.3390/toxins9020065 - 14 Feb 2017

Cited by 11 | Viewed by 4530

Abstract

Recently a species in the genus Talaromyces, a uniseriate species of Aspergillus section Nigri and an isolate each of two widespread species, Penicillium rubens and P. commune, were reported to produce ochratoxin A. This claim was based on insufficient biological and [...] Read more.

Recently a species in the genus Talaromyces, a uniseriate species of Aspergillus section Nigri and an isolate each of two widespread species, Penicillium rubens and P. commune, were reported to produce ochratoxin A. This claim was based on insufficient biological and chemical data. We propose a list of criteria that need to be met before an unexpected mycotoxin producer is reported. There have only been convincing data on ochratoxin A production for Penicillium verrucosum, P. nordicum, P. thymicola, all from Penicillium series Verrucosa, and from species in three sections of Aspergillus: section Circumdati, section Nigri and section Flavi. Full article

2016

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Open AccessArticle

Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

by Liye Zhu, Tao Yu, Xiaozhe Qi, Jing Gao, Kunlun Huang, Xiaoyun He, Haoshu Luo and Wentao Xu

Toxins 2016, 8(12), 373; https://doi.org/10.3390/toxins8120373 - 14 Dec 2016

Cited by 36 | Viewed by 5757

Abstract

Ochratoxin A (OTA) displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage [...] Read more.

Ochratoxin A (OTA) displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD) and livers (SOD and GSH). DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model. Full article

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Open AccessArticle

Screening and Identification of Novel Ochratoxin A-Producing Fungi from Grapes

by Xiaoyun Zhang, Yulin Li, Haiying Wang, Xiangyu Gu, Xiangfeng Zheng, Yun Wang, Junwei Diao, Yaping Peng and Hongyin Zhang

Toxins 2016, 8(11), 333; https://doi.org/10.3390/toxins8110333 - 12 Nov 2016

Cited by 30 | Viewed by 6138

Abstract

Ochratoxin A (OTA) contamination has been established as a world-wide problem. In this study, the strains with the ability of OTA production were screened by analyzing the green fluorescence of the isolates colonies from the grapes in Zhenjiang with 365 nm UV light [...] Read more.

Ochratoxin A (OTA) contamination has been established as a world-wide problem. In this study, the strains with the ability of OTA production were screened by analyzing the green fluorescence of the isolates colonies from the grapes in Zhenjiang with 365 nm UV light and confirmed by HPLC with fluorescent detection (HPLC-FLD). The results showed that seven isolates acquired the characteristic of the fluorescence, of which only five showed the ability of OTA production as confirmed by HPLC-FLD analysis. The five OTA-producing strains were identified based on comparative sequence analysis of three conserved genes (ITS, BenA and RPB2) of the strains, and they are Talaromyces rugulosus (O1 and Q3), Penicillium commune (V5-1), Penicillium rubens (MQ-5) and Aspergillus aculeatus (MB1-1). There are two Penicillium species of the five OTA-producing strains and our study is the first to report that P. rubens, T. rugulosus and A. aculeatus can produce OTA. This work would contribute to comprehensively understanding the fungi with an OTA-producing ability in grapes before harvest and then take effective measures to prevent OTA production. Full article

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Open AccessReview

Ochratoxin A: 50 Years of Research

by Frantisek Malir, Vladimir Ostry, Annie Pfohl-Leszkowicz, Jan Malir and Jakub Toman

Toxins 2016, 8(7), 191; https://doi.org/10.3390/toxins8070191 - 4 Jul 2016

Cited by 350 | Viewed by 26745

Abstract

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but [...] Read more.

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans. Full article

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Open AccessReview

Ochratoxin A: Molecular Interactions, Mechanisms of Toxicity and Prevention at the Molecular Level

by Tamás Kőszegi and Miklós Poór

Toxins 2016, 8(4), 111; https://doi.org/10.3390/toxins8040111 - 15 Apr 2016

Cited by 239 | Viewed by 21982

Abstract

Ochratoxin A (OTA) is a widely-spread mycotoxin all over the world causing major health risks. The focus of the present review is on the molecular and cellular interactions of OTA. In order to get better insight into the mechanism of its toxicity and [...] Read more.

Ochratoxin A (OTA) is a widely-spread mycotoxin all over the world causing major health risks. The focus of the present review is on the molecular and cellular interactions of OTA. In order to get better insight into the mechanism of its toxicity and on the several attempts made for prevention or attenuation of its toxic action, a detailed description is given on chemistry and toxicokinetics of this mycotoxin. The mode of action of OTA is not clearly understood yet, and seems to be very complex. Inhibition of protein synthesis and energy production, induction of oxidative stress, DNA adduct formation, as well as apoptosis/necrosis and cell cycle arrest are possibly involved in its toxic action. Since OTA binds very strongly to human and animal albumin, a major emphasis is done regarding OTA-albumin interaction. Displacement of OTA from albumin by drugs and by natural flavonoids are discussed in detail, hypothesizing their potentially beneficial effect in order to prevent or attenuate the OTA-induced toxic consequences. Full article

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Open AccessArticle

Maternal-Fetal Cancer Risk Assessment of Ochratoxin A during Pregnancy

by Chit Shing Jackson Woo and Hani El-Nezami

Toxins 2016, 8(4), 87; https://doi.org/10.3390/toxins8040087 - 23 Mar 2016

Cited by 19 | Viewed by 6043

Abstract

Increasing evidence has demonstrated that in utero exposure to environmental chemicals may interfere with fetal development and increase the risk of disease and cancer development later in life. Ochratoxin A (OTA) has been proven to induce diverse toxic effects including teratogenicity, carcinogenicity, immunotoxicity [...] Read more.

Increasing evidence has demonstrated that in utero exposure to environmental chemicals may interfere with fetal development and increase the risk of disease and cancer development later in life. Ochratoxin A (OTA) has been proven to induce diverse toxic effects including teratogenicity, carcinogenicity, immunotoxicity and potential endocrine disruption. Due to the continuous and widespread occurrence of OTA as a potential contaminant of staple foods, there is increasing concern of in utero exposure of fetus to this mycotoxin. In this study, maternal-fetal risk assessment of OTA during pregnancy was conducted using the benchmark dose approach for genotoxic carcinogens. The daily intake of OTA for Egyptian pregnant women was estimated based on their serum OTA level using the refined Klaassen equation for pregnancy. Fetal exposure level was also estimated based on the maternal data. Comparison between the estimated daily exposure and the negligible cancer risk intake (NCRI), and the calculation of margin of exposure (MOE) implicated that OTA exposure from dietary intake would be of low health concern for this general subpopulation of Egyptian women. This subpopulation of pregnant women was generally estimated not to be in high-risk for toxicity induced by OTA. Full article

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Open AccessReview

Ochratoxin A Producing Fungi, Biosynthetic Pathway and Regulatory Mechanisms

by Yan Wang, Liuqing Wang, Fei Liu, Qi Wang, Jonathan Nimal Selvaraj, Fuguo Xing, Yueju Zhao and Yang Liu

Toxins 2016, 8(3), 83; https://doi.org/10.3390/toxins8030083 - 21 Mar 2016

Cited by 149 | Viewed by 9972

Abstract

Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked [...] Read more.

Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes of the biosynthetic pathway. We discuss recent information on molecular studies of OTA biosynthesis despite insufficient genetic background in detail. Accordingly, genetic regulation has also been explored with regard to the interaction between the regulators and the environmental factors. In this review, we focus on three aspects of OTA: OTA-producing strains, OTA biosynthetic pathway and the regulation mechanisms of OTA production. This can pave the way to assist in protecting food and feed from OTA contamination by understanding OTA biosynthetic pathway and regulatory mechanisms. Full article

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Open AccessFeature PaperArticle

Teratogenicity of Ochratoxin A and the Degradation Product, Ochratoxin α, in the Zebrafish (Danio rerio) Embryo Model of Vertebrate Development

by Mehreen Haq, Nelson Gonzalez, Keenan Mintz, Asha Jaja-Chimedza, Christopher Lawrence De Jesus, Christina Lydon, Aaron Z. Welch and John P. Berry

Toxins 2016, 8(2), 40; https://doi.org/10.3390/toxins8020040 - 5 Feb 2016

Cited by 50 | Viewed by 7671

Abstract

Ochratoxins, and particularly ochratoxin A (OTA), are toxic fungal-derived contaminants of food and other agricultural products. Growing evidence supports the degradation of OTA by chemical, enzymatic and/or microbial means as a potential approach to remove this mycotoxin from food products. In particular, hydrolysis [...] Read more.

Ochratoxins, and particularly ochratoxin A (OTA), are toxic fungal-derived contaminants of food and other agricultural products. Growing evidence supports the degradation of OTA by chemical, enzymatic and/or microbial means as a potential approach to remove this mycotoxin from food products. In particular, hydrolysis of OTA to ochratoxin α (OTα) and phenylalanine is the presumptive product of degradation in most cases. In the current study, we employed the zebrafish (Danio rerio) embryo, as a model of vertebrate development to evaluate, the teratogenicity of OTA and OTα. These studies show that OTA is potently active in the zebrafish embryo toxicity assay (ZETA), and that toxicity is both concentration- and time-dependent with discernible and quantifiable developmental toxicity observed at nanomolar concentrations. On the other hand, OTα had no significant effect on embryo development at all concentrations tested supporting a decreased toxicity of this degradation product. Taken together, these results suggest that ZETA is a useful, and highly sensitive, tool for evaluating OTA toxicity, as well as its degradation products, toward development of effective detoxification strategies. Specifically, the results obtained with ZETA, in the present study, further demonstrate the toxicity of OTA, and support its degradation via hydrolysis to OTα as an effective means of detoxification. Full article

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2015

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Open AccessReview

Comparative Ochratoxin Toxicity: A Review of the Available Data

by Alexandra H. Heussner and Lewis E. H. Bingle

Toxins 2015, 7(10), 4253-4282; https://doi.org/10.3390/toxins7104253 - 22 Oct 2015

Cited by 257 | Viewed by 13153

Abstract

Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA), the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious [...] Read more.

Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA), the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious health issue and has been associated with several human and animal diseases including poultry ochratoxicosis, porcine nephropathy, human endemic nephropathies and urinary tract tumours in humans. More than 30 years ago, OTA was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate its mode of action, however, this is still under debate. OTA is regarded as the most toxic family member, however, other ochratoxins or their metabolites and, in particular, ochratoxin mixtures or combinations with other mycotoxins may represent serious threats to human and animal health. This review summarises and evaluates current knowledge about the differential and comparative toxicity of the ochratoxin group. Full article

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Open AccessReview

Man-Made Synthetic Receptors for Capture and Analysis of Ochratoxin A

by Claudio Baggiani, Cristina Giovannoli and Laura Anfossi

Toxins 2015, 7(10), 4083-4098; https://doi.org/10.3390/toxins7104083 - 10 Oct 2015

Cited by 14 | Viewed by 5793

Abstract

Contemporary analytical methods have the sensitivity required for Ochratoxin A detection and quantification, but direct application of these methods on real samples can be rarely performed because of matrix complexity. Thus, efficient sample pre-treatment methods are needed. Recent years have seen the increasing [...] Read more.

Contemporary analytical methods have the sensitivity required for Ochratoxin A detection and quantification, but direct application of these methods on real samples can be rarely performed because of matrix complexity. Thus, efficient sample pre-treatment methods are needed. Recent years have seen the increasing use of artificial recognition systems as a viable alternative to natural receptors, because these materials seem to be particularly suitable for applications where selectivity for Ochratoxin A is essential. In this review, molecularly imprinted polymers, aptamers and tailor-made peptides for Ochratoxin A capture and analysis with particular attention to solid phase extraction applications will be discussed. Full article

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Open AccessArticle

Ochratoxin A Dietary Exposure of Ten Population Groups in the Czech Republic: Comparison with Data over the World

by Vladimir Ostry, Frantisek Malir, Marcela Dofkova, Jarmila Skarkova, Annie Pfohl-Leszkowicz and Jiri Ruprich

Toxins 2015, 7(9), 3608-3635; https://doi.org/10.3390/toxins7093608 - 10 Sep 2015

Cited by 51 | Viewed by 6561

Abstract

Ochratoxin A is a nephrotoxic and renal carcinogenic mycotoxin and is a common contaminant of various food commodities. Eighty six kinds of foodstuffs (1032 food samples) were collected in 2011–2013. High-performance liquid chromatography with fluorescence detection was used for ochratoxin A determination. Limit [...] Read more.

Ochratoxin A is a nephrotoxic and renal carcinogenic mycotoxin and is a common contaminant of various food commodities. Eighty six kinds of foodstuffs (1032 food samples) were collected in 2011–2013. High-performance liquid chromatography with fluorescence detection was used for ochratoxin A determination. Limit of quantification of the method varied between 0.01–0.2 μg/kg depending on the food matrices. The most exposed population is children aged 4–6 years old. Globally for this group, the maximum ochratoxin A dietary exposure for “average consumer” was estimated at 3.3 ng/kg bw/day (lower bound, considering the analytical values below the limit of quantification as 0) and 3.9 ng/kg bw/day (middle bound, considering the analytical values below the limit of quantification as 1/2 limit of quantification). Important sources of exposure for this latter group include grain-based products, confectionery, meat products and fruit juice. The dietary intake for “high consumers” in the group 4–6 years old was estimated from grains and grain-based products at 19.8 ng/kg bw/day (middle bound), from tea at 12.0 ng/kg bw/day (middle bound) and from confectionery at 6.5 ng/kg bw/day (middle bound). For men aged 18–59 years old beer was the main contributor with an intake of 2.60 ng/kg bw/day (“high consumers”, middle bound). Tea and grain-based products were identified to be the main contributors for dietary exposure in women aged 18–59 years old. Coffee and wine were identified as a higher contributor of the OTA intake in the population group of women aged 18–59 years old compared to the other population groups. Full article

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Open AccessCommunication

Saccharomyces Cerevisiae Cell Wall Components as Tools for Ochratoxin A Decontamination

by Małgorzata Piotrowska and Anna Masek

Toxins 2015, 7(4), 1151-1162; https://doi.org/10.3390/toxins7041151 - 2 Apr 2015

Cited by 71 | Viewed by 7640

Abstract

The aim of this study was to evaluate the usefulness of Saccharomyces cerevisiae cell wall preparations in the adsorption of ochratoxin A (OTA). The study involved the use of a brewer’s yeast cell wall devoid of protein substances, glucans obtained by water and [...] Read more.

The aim of this study was to evaluate the usefulness of Saccharomyces cerevisiae cell wall preparations in the adsorption of ochratoxin A (OTA). The study involved the use of a brewer’s yeast cell wall devoid of protein substances, glucans obtained by water and alkaline extraction, a glucan commercially available as a dietary supplement for animals and, additionally, dried brewer’s yeast for comparison. Fourier Transform Infrared (FTIR) analysis of the obtained preparations showed bands characteristic for glucans in the resulting spectra. The yeast cell wall preparation, water-extracted glucan and the commercial glucan bound the highest amount of ochratoxin A, above 55% of the initial concentration, and the alkaline-extracted glucan adsorbed the lowest amount of this toxin. It has been shown that adsorption is most effective at a close-to-neutral pH, while being considerably limited in alkaline conditions. Full article

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Open AccessCommunication

Detection of Ochratoxin a Using Molecular Beacons and Real-Time PCR Thermal Cycler

by Simona Marianna Sanzani, Massimo Reverberi, Corrado Fanelli and Antonio Ippolito

Toxins 2015, 7(3), 812-820; https://doi.org/10.3390/toxins7030812 - 9 Mar 2015

Cited by 33 | Viewed by 6873

Abstract

We developed a simple and cheap assay for quantitatively detecting ochratoxin A (OTA) in wine. A DNA aptamer available in literature was used as recognition probe in its molecular beacon form, i.e., with a fluorescence-quenching pair at the stem ends. Our aptabeacon [...] Read more.

We developed a simple and cheap assay for quantitatively detecting ochratoxin A (OTA) in wine. A DNA aptamer available in literature was used as recognition probe in its molecular beacon form, i.e., with a fluorescence-quenching pair at the stem ends. Our aptabeacon could adopt a conformation allowing OTA binding, causing a fluorescence rise due to the increased distance between fluorophore and quencher. We used real-time PCR equipment for capturing the signal. With this assay, under optimized conditions, the entire process can be completed within 1 h. In addition, the proposed system exhibited a good selectivity for OTA against other mycotoxins (ochratoxin B and aflatoxin M1) and limited interference from aflatoxin B1 and patulin. A wide linear detection range (0.2–2000 µM) was achieved, with LOD = 13 nM, r = 0.9952, and R² = 0.9904. The aptabeacon was also applied to detect OTA in red wine spiked with the same dilution series. A linear correlation with a LOD = 19 nM, r = 0.9843, and R² = 0.9708 was observed, with recoveries in the range 63%–105%. Intra- and inter-day assays confirmed its reproducibility. The proposed biosensor, although still being finalized, might significantly facilitate the quantitative detection of OTA in wine samples, thus improving their quality control from a food safety perspective. Full article

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2014

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Open AccessReview

A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity

by Alice Limonciel and Paul Jennings

Toxins 2014, 6(1), 371-379; https://doi.org/10.3390/toxins6010371 - 20 Jan 2014

Cited by 108 | Viewed by 10832

Abstract

Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II [...] Read more.

Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II metabolism inducibility. The effects combined would render the cell and tissue more vulnerable to oxidative stress. Indeed, Nrf2 knock out animals exhibit increased susceptibility to various types of chemical-induced injury. Several studies have shown that OTA exposure can inhibit Nrf2 responses. Such an action would initially lead to increased susceptibility to both physiological and chemical-induced cell stress. However, chronic exposure to OTA may also act as a selective pressure for somatic mutations in Nrf2 or its inhibitor Keap-1, leading to constitutive Nrf2 activation. Nrf2 overexpression confers a survival advantage and is often associated with cancer cell survival. Here we review the evidence for OTA’s role as an Nrf2 inhibitor and discuss the implications of this mechanism in nephrotoxicity and carcinogenicity. Full article

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2013

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Open AccessArticle

In Vitro Glucuronidation of Ochratoxin A by Rat Liver Microsomes

by Zheng Han, Emmanuel K. Tangni, José Diana Di Mavungu, Lynn Vanhaecke, Sarah De Saeger, Aibo Wu and Alfons Callebaut

Toxins 2013, 5(12), 2671-2685; https://doi.org/10.3390/toxins5122671 - 18 Dec 2013

Cited by 21 | Viewed by 8643

Abstract

Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid [...] Read more.

Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), UHPLC-Orbitrap-high resolution mass spectrometry (HRMS) and liquid chromatography-multiple stage mass spectrometry (LC-MSⁿ) were utilized to investigate the metabolic profile of OTA in rat liver microsomes. Three conjugated products of OTA corresponding to amino-, phenol- and acyl-glucuronides were identified, and the related structures were confirmed by hydrolysis with β-glucuronidase. Moreover, OTA methyl ester, OTα and OTα-glucuronide were also found in the reaction solution. Based on these results, an in vitro metabolic pathway of OTA has been proposed for the first time. Full article

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Open AccessArticle

Impact of pH on the Stability and the Cross-Reactivity of Ochratoxin A and Citrinin

by Ingrid Bazin, Virginie Faucet-Marquis, Marie-Carmen Monje, Micheline El Khoury, Jean-Louis Marty and Annie Pfohl-Leszkowicz

Toxins 2013, 5(12), 2324-2340; https://doi.org/10.3390/toxins5122324 - 28 Nov 2013

Cited by 39 | Viewed by 8798

Abstract

Mycotoxins are secondary metabolites produced by several fungi contaminating crops. In several countries, the maximum permitted levels of mycotoxins are found in foodstuffs and feedstuffs. The common strategy of mycotoxin analysis involves extraction, clean-up and quantification by chromatography. In this paper, we analyzed [...] Read more.

Mycotoxins are secondary metabolites produced by several fungi contaminating crops. In several countries, the maximum permitted levels of mycotoxins are found in foodstuffs and feedstuffs. The common strategy of mycotoxin analysis involves extraction, clean-up and quantification by chromatography. In this paper, we analyzed the reasons of underestimation of ochratoxin A (OTA) content in wine, and overestimation of OTA in wheat, depending on the pH of the clean-up step and the simultaneous presence of citrinin (CIT). We demonstrated that the increase of pH by adding polyethylene glycol (PEG) to wine led to an underestimation of OTA by conversion of OTA into open ring ochratoxin A OP-OA. In comparing three methods of extraction and clean-up for the determination of OTA and CIT in wheat—(i) an inter-laboratory validated method for OTA in cereals using immunoaffinity column clean-up (IAC) and extraction by acetonitrile/water; (ii) a validated method using IAC and extraction with 1% bicarbonate Na; and (iii) an in-house validated method based on acid liquid/liquid extraction—we observed an overestimation of OTA after immunoaffinity clean-up when CIT is also present in the sample, whereas an underestimation was observed when OTA was alone. Under neutral and alkaline conditions, CIT was partially recognized by OTA antibodies. Full article

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Open AccessReview

Aptamers: A Promising Tool for Ochratoxin A Detection in Food Analysis

by Amina Rhouati, Cheng Yang, Akhtar Hayat and Jean-Louis Marty

Toxins 2013, 5(11), 1988-2008; https://doi.org/10.3390/toxins5111988 - 5 Nov 2013

Cited by 113 | Viewed by 11000

Abstract

The contamination of food and feed by mycotoxins has become an increasingly serious problem. Mycotoxins represent a major risk to human and animal health, as well as economics. Herein, we focus on Ochratoxin A (OTA), which is one of the most common mycotoxins [...] Read more.

The contamination of food and feed by mycotoxins has become an increasingly serious problem. Mycotoxins represent a major risk to human and animal health, as well as economics. Herein, we focus on Ochratoxin A (OTA), which is one of the most common mycotoxins contaminating feed and foodstuffs. OTA is a secondary metabolite produced by various Aspergillus and Penicillium strains. Upon ingestion, OTA has a number of acute and chronic toxic effects. It is nephrotoxic, teratogenic, immunosuppressive, and carcinogenic (group 2B). As a consequence, some regulatory limits have been introduced on the levels of OTA in several commodities. The toxic nature of OTA demands highly sensitive and selective monitoring techniques to protect human and animal health. As alternative to traditional analytical techniques, biochemical methods for OTA analysis have attained great interest in the last few decades. They are mainly based on the integration of antibodies or aptamers as biorecognition elements in sensing platforms. However, aptamers have gained more attention in affinity-based assays because of their high affinity, specificity, stability, and their easy chemical synthesis. In this brief review, we present an overview of aptamer-based assays and their applications in OTA purification and detection, appeared in the literature in the last five years. Full article

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Open AccessReview

Deleterious Effects of Mycotoxin Combinations Involving Ochratoxin A

by Maja Šegvić Klarić, Dubravka Rašić and Maja Peraica

Toxins 2013, 5(11), 1965-1987; https://doi.org/10.3390/toxins5111965 - 1 Nov 2013

Cited by 95 | Viewed by 9901

Abstract

Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than [...] Read more.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than one mycotoxin, earlier studies focused on the occurrence and toxicology of only OTA. Only a limited number of surveys showed that OTA co-occurs in food with mycotoxins (citrinin-CIT, penicilic acid, fumonisin B₁-FB₁, aflatoxins-AF) which exert nephrotoxic, carcinogenic or carcinogen-promoting activity. This review summarises the findings on OTA and its co-occurrence with the mentioned mycotoxins in food as well as experimental data on their combined toxicity. Most of the tested mycotoxin mixtures involving OTA produced additive or synergistic effects in experimental models suggesting that these combinations represent a significant health hazard. Special attention should be given to mixtures that include carcinogenic and cancer-promoting mycotoxins. Full article

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Open AccessArticle

Comparison of Clean-Up Methods for Ochratoxin A on Wine, Beer, Roasted Coffee and Chili Commercialized in Italy

by Ambra Prelle, Davide Spadaro, Aleksandra Denca, Angelo Garibaldi and Maria Lodovica Gullino

Toxins 2013, 5(10), 1827-1844; https://doi.org/10.3390/toxins5101827 - 22 Oct 2013

Cited by 37 | Viewed by 7966

Abstract

The most common technique used to detect ochratoxin A (OTA) in food matrices is based on extraction, clean-up, and chromatography detection. Different clean-up cartridges, such as immunoaffinity columns (IAC), molecular imprinting polymers (MIP), Mycosep™ 229, Mycospin™, and Oasis^® HLB (Hydrophilic Lipophilic balance) [...] Read more.

The most common technique used to detect ochratoxin A (OTA) in food matrices is based on extraction, clean-up, and chromatography detection. Different clean-up cartridges, such as immunoaffinity columns (IAC), molecular imprinting polymers (MIP), Mycosep™ 229, Mycospin™, and Oasis^® HLB (Hydrophilic Lipophilic balance) as solid phase extraction were tested to optimize the purification for red wine, beer, roasted coffee and chili. Recovery, reproducibility, reproducibility, limit of detection (LOD) and limit of quantification (LOQ) were calculated for each clean-up method. IAC demonstrated to be suitable for OTA analysis in wine and beer with recovery rate >90%, as well as Mycosep™ for wine and chili. On the contrary, MIP columns were the most appropriate to clean up coffee. A total of 120 samples (30 wines, 30 beers, 30 roasted coffee, 30 chili) marketed in Italy were analyzed, by applying the developed clean-up methods. Twenty-seven out of 120 samples analyzed (22.7%: two wines, five beers, eight coffees, and 12 chili) resulted positive to OTA. A higher incidence of OTA was found in chili (40.0%) more than wine (6.6%), beers (16.6%) and coffee (26.6%). Moreover, OTA concentration in chili was the highest detected, reaching 47.8 µg/kg. Furthermore, three samples (2.5%), two wines and one chili, exceeded the European threshold. Full article

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Open AccessReview

Toxicity of Ochratoxin A and Its Modulation by Antioxidants: A Review

by Valeria Sorrenti, Claudia Di Giacomo, Rosaria Acquaviva, Ignazio Barbagallo, Matteo Bognanno and Fabio Galvano

Toxins 2013, 5(10), 1742-1766; https://doi.org/10.3390/toxins5101742 - 11 Oct 2013

Cited by 163 | Viewed by 11568

Abstract

Ochratoxin A (OTA) is a mycotoxin involved in the development of different types of cancers in rats, mice and humans. A growing number of in vitro and in vivo studies has been collected and has described evidence compatible with a role for oxidative [...] Read more.

Ochratoxin A (OTA) is a mycotoxin involved in the development of different types of cancers in rats, mice and humans. A growing number of in vitro and in vivo studies has been collected and has described evidence compatible with a role for oxidative stress in OTA toxicity and carcinogenicity. Because the contribution of the oxidative stress response in the development of cancers is well established, a role in OTA carcinogenicity is plausible. Several studies have been performed to try to counteract the adverse effects of oxygen radicals generated under OTA-exposure. A number of molecules with various antioxidant properties were tested, using in vivo or in vitro models. Protection against OTA-induced DNA damage, lipid peroxidation, as well as cytotoxicity were observed, further confirming the link between OTA toxicity and oxidative damage. These studies demonstrated that antioxidants are able to counteract the deleterious effects of chronic consumption or exposure to OTA and confirmed the potential effectiveness of dietary strategies to counteract OTA toxicity. Full article

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Open AccessReview

Porcine/Chicken or Human Nephropathy as the Result of Joint Mycotoxins Interaction

by Stoycho D. Stoev and Stefan A. Denev

Toxins 2013, 5(9), 1503-1530; https://doi.org/10.3390/toxins5091503 - 4 Sep 2013

Cited by 20 | Viewed by 8736

Abstract

A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific [...] Read more.

A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific conditions for their growth and toxins production were briefly described. A survey was made about the most frequent nephrotoxic fungal contaminants in various feedstuffs from plant origin. In addition, their natural quantities and importance for development of mycotoxic porcine/chick nephropathy (MPN/MCN) are also explored. In addition, a survey was made of the feedstuffs representing the most favorable environment for nephrotoxic fungal growth as well as the most favorable storehouse conditions for this fungal growth were shortly described. The significance of some underestimated fungal species, which can provoke kidney damage, was studied. The importance of joint mycotoxin interaction and newly identified fungal metabolites in the complex etiology of mycotoxic nephropathy ranged in some countries is deeply investigated. The toxicity of the low contamination levels of some combinations of mycotoxins often administered by pigs and chicks in the practice was carefully studied. Full article

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Open AccessArticle

Differences in the Regulation of Ochratoxin A by the HOG Pathway in Penicillium and Aspergillus in Response to High Osmolar Environments

by Dominic Stoll, Markus Schmidt-Heydt and Rolf Geisen

Toxins 2013, 5(7), 1282-1298; https://doi.org/10.3390/toxins5071282 - 19 Jul 2013

Cited by 42 | Viewed by 6876

Abstract

Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three important ochratoxin A producing species. P. verrucosum is in addition able to produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl rich environments like salt rich dry cured [...] Read more.

Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three important ochratoxin A producing species. P. verrucosum is in addition able to produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl rich environments like salt rich dry cured foods or even salines. In this organism, the biosynthesis of ochratoxin A plays an adaptive role in this habitat. P. verrucosum generally can be found on cereals, but occasionally also on salt rich dry cured foods. In contrast A. carbonarius usually cannot be found in NaCl rich environments, but it occurs in another environment with high concentration of solutes, e.g., in sugar rich substrates like grapes and grape juices. Usually osmotic challenging conditions activate the HOG MAP kinase signal cascade, which in turn activates various osmo-regulated genes. In the current analysis, it could be demonstrated that in case of P. nordicum and P. verrucosum the NaCl induced production of ochratoxin A is correlated to the phosphorylation status of the HOG MAP kinase. Just the opposite was true for A. carbonarius. In this case, also higher amounts of NaCl in the medium lead to an increased phosphorylation status of HOG, but no increase in ochratoxin biosynthesis was observed. In contrast to the Penicillia, higher NaCl concentrations lead to a rapid cessation of growth by A. carbonarius. High glucose concentrations have much less impact on growth and the phosphorylation of HOG. Full article

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Open AccessArticle

Computational Design of Peptide Ligands for Ochratoxin A

by Meike Heurich, Zeynep Altintas and Ibtisam E. Tothill

Toxins 2013, 5(6), 1202-1218; https://doi.org/10.3390/toxins5061202 - 21 Jun 2013

Cited by 38 | Viewed by 8946

Abstract

In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA). A virtual library of 20 natural amino acids was used as building blocks to design a [...] Read more.

In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA). A virtual library of 20 natural amino acids was used as building blocks to design a short peptide library against ochratoxin A template using the de novo design program, LeapFrog, and the dynamic modelling software, FlexiDock. Peptide sequences were ranked according to calculated binding scores in their capacity to bind to ochratoxin A. Two high scoring peptides with the sequences N'-Cys-Ser-Ile-Val-Glu-Asp-Gly-Lys-C' (octapeptide) and N'-Gly-Pro-Ala-Gly-Ile-Asp-Gly-Pro-Ala-Gly-Ile-Arg-Cys-C' (13-mer) were selected for synthesis from the resulting database. These synthesized peptides were characterized using a microtitre plate-based binding assay and a surface plasmon resonance biosensor (Biacore 3000). The binding assay confirmed that both de novo designed peptides did bind to ochratoxin A in vitro. SPR analysis confirmed that the peptides bind to ochratoxin A, with calculated K_D values of ~15.7 μM (13-mer) and ~11.8 μM (octamer). The affinity of the peptides corresponds well with the molecular modelling results, as the 13-mer peptide affinity is about 1.3-times weaker than the octapeptide; this is in accordance with the binding energy values modelled by FlexiDock. This work illustrates the potential of using computational modelling to design a peptide sequence that exhibits in vitro binding affinity for a small molecular weight toxin. Full article

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Open AccessArticle

First Evidence of Placental Transfer of Ochratoxin A in Horses

by Fiorenza Minervini, Alessandra Giannoccaro, Michele Nicassio, Giuseppe Panzarini and Giovanni Michele Lacalandra

Toxins 2013, 5(1), 84-92; https://doi.org/10.3390/toxins5010084 - 11 Jan 2013

Cited by 24 | Viewed by 6903

Abstract

Ochratoxin A (OTA) is a renal mycotoxin and transplacental genotoxic carcinogen. The aim of this study was to evaluate the natural occurrence of OTA in equine blood samples and its placental transfer. For the assessment of OTA levels, serum samples were collected from [...] Read more.

Ochratoxin A (OTA) is a renal mycotoxin and transplacental genotoxic carcinogen. The aim of this study was to evaluate the natural occurrence of OTA in equine blood samples and its placental transfer. For the assessment of OTA levels, serum samples were collected from 12 stallions, 7 cycling mares and 17 pregnant mares. OTA was found in 83% of serum samples (median value = 121.4 pg/mL). For the assessment of placental transfer, serum samples were collected from the 17 mares after delivery and from the umbilical cords of their foals, after foaling. Fourteen serum samples from pregnant mares contained OTA (median value = 106.5 pg/mL), but only 50% of their foals were exposed (median values = 96.6 pg/mL). HPLC analysis carried out on four serum samples (collected from two mares and their respective foals) supported the ELISA results on OTA placental transfer. This is the first report on the natural occurrence of OTA in horse serum samples and placental transfer in horses. Full article

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Open AccessArticle

Ochratoxin A Management in Vineyards by Lobesia botrana Biocontrol

by Giuseppe Cozzi, Stefania Somma, Miriam Haidukowski and Antonio F. Logrieco

Toxins 2013, 5(1), 49-59; https://doi.org/10.3390/toxins5010049 - 2 Jan 2013

Cited by 31 | Viewed by 7298

Abstract

Grape berries attacked by Lobesia botrana larvae are more easily infected by Aspergillus section Nigri (black aspergilli) ochratoxigenic species. Two-year field trials were carried out in Apulia (Italy) to evaluate a bioinsecticide control strategy against L. botrana and the indirect effect on reducing [...] Read more.

Grape berries attacked by Lobesia botrana larvae are more easily infected by Aspergillus section Nigri (black aspergilli) ochratoxigenic species. Two-year field trials were carried out in Apulia (Italy) to evaluate a bioinsecticide control strategy against L. botrana and the indirect effect on reducing ochratoxin A (OTA) contamination in vineyards. A commercial Bacillus thuringiensis formulate and an experimental Beauveria bassiana (ITEM-1559) formulate were tested in two vineyards cultivated with the same grape variety, Negroamaro, but with two different training systems (espalier and little-arbor techniques). In both years and training systems the treatments by B. bassiana ITEM-1559 significantly controlled L. botrana larvae attacks with effectiveness similar to B. thuringensis (more than 20%). A significant reduction of OTA concentrations (up to 80% compared to untreated controls) was observed only in the first year in both training systems, when the metereological parameters prior to harvest were more favorable to the insect attack. Results of field trials showed that B. bassiana ITEM-1559 is a valid bioinsecticide against L. botrana and that grape moth biocontrol is a strategy to reduce OTA contamination in vineyard in seasons with heavy natural infestation. Full article

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Open AccessArticle

Wavelength-Dependent Degradation of Ochratoxin and Citrinin by Light in Vitro and in Vivo and Its Implications on Penicillium

by Markus Schmidt-Heydt, Benedikt Cramer, Irina Graf, Sandra Lerch, Hans-Ulrich Humpf and Rolf Geisen

Toxins 2012, 4(12), 1535-1551; https://doi.org/10.3390/toxins4121535 - 14 Dec 2012

Cited by 41 | Viewed by 9417

Abstract

It has previously been shown that the biosynthesis of the mycotoxins ochratoxin A and B and of citrinin by Penicillium is regulated by light. However, not only the biosynthesis of these mycotoxins, but also the molecules themselves are strongly affected by light of [...] Read more.

It has previously been shown that the biosynthesis of the mycotoxins ochratoxin A and B and of citrinin by Penicillium is regulated by light. However, not only the biosynthesis of these mycotoxins, but also the molecules themselves are strongly affected by light of certain wavelengths. The white light and blue light of 470 and 455 nm are especially able to degrade ochratoxin A, ochratoxin B and citrinin after exposure for a certain time. After the same treatment of the secondary metabolites with red (627 nm), yellow (590 nm) or green (530 nm) light or in the dark, almost no degradation occurred during that time indicating the blue light as the responsible part of the spectrum. The two derivatives of ochratoxin (A and B) are degraded to certain definitive degradation products which were characterized by HPLC-FLD-FTMS. The degradation products of ochratoxin A and B did no longer contain phenylalanine however were still chlorinated in the case of ochratoxin A. Citrinin is completely degraded by blue light. A fluorescent band was no longer visible after detection by TLC suggesting a higher sensitivity and apparently greater absorbance of energy by citrinin. The fact that especially blue light degrades the three secondary metabolites is apparently attributed to the absorption spectra of the metabolites which all have an optimum in the short wave length range. The absorption range of citrinin is, in particular, broader and includes the wave length of blue light. In wheat, which was contaminated with an ochratoxin A producing culture of Penicillium verrucosum and treated with blue light after a pre-incubation by the fungus, the concentration of the preformed ochratoxin A reduced by roughly 50% compared to the control and differed by > 90% compared to the sample incubated further in the dark. This indicates that the light degrading effect is also exerted in vivo, e.g., on food surfaces. The biological consequences of the light instability of the toxins are discussed. Full article

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Open AccessArticle

Apoptosis Induction by OTA and TNF-α in Cultured Primary Rat Hepatocytes and Prevention by Silibinin

by Ebtisam Essid, Yousef Dernawi and Ernst Petzinger

Toxins 2012, 4(11), 1139-1156; https://doi.org/10.3390/toxins4111139 - 2 Nov 2012

Cited by 24 | Viewed by 7369

Abstract

In cultures of primary rat hepatocytes, apoptosis occurred after application of 20 ng/mL tumor necrosis factor alpha (TNF-α). However, this was only in the presence of 200 ng/mL of the transcriptional inhibitor actinomycin D (ActD). This toxic effect was completely prevented in the [...] Read more.

In cultures of primary rat hepatocytes, apoptosis occurred after application of 20 ng/mL tumor necrosis factor alpha (TNF-α). However, this was only in the presence of 200 ng/mL of the transcriptional inhibitor actinomycin D (ActD). This toxic effect was completely prevented in the presence of 25 µg/mL soluble TNF-α receptor I (sTNFR I) in the supernatant of hepatocyte cell cultures. Apoptosis also occurred after application of 12.5 µmol/L ochratoxin A (OTA). However, that was not prevented by up to 500 µg/mL sTNFR I, indicating that TNF-α/TNFR I is not involved in OTA mediated apoptosis in hepatocytes. The antioxidative flavanolignan silibinin in doses from 130 to 260 µmol/L prevented chromatin condensation, caspase-3 activation, and apoptotic DNA fragmentation that were induced by OTA, by 10 mmol/L hydrogen peroxide (H₂O₂) and by ultraviolet (UV-C) light (50 mJ/cm²), respectively. To achieve protection by silibinin, the drug was applied to the cell cultures for 2 h in advance. OTA stimulated lipid peroxidation on cultured immortalized rat liver HPCT cells, as was revealed by malondialdehyde (MDA) production. Lipid peroxidation occurred further by H₂O₂ and ActD/TNF-α incubation. These reactions were also suppressed by silibinin pretreatment. We conclude that the anti-apoptotic activity of silibinin against OTA, H₂O₂ and ActD/ TNF-α is caused in vitro by the antioxidative effects of the flavanolignan. Furthermore, cytotoxicity of the pro-apoptotic toxins was revealed by MTT-test. When applied separately, ActD and TNF-α showed no cytotoxic effects after 24 h, but were cytotoxic if applied in combination. The used concentrations of OTA, H₂O₂ and the dose of UV-C caused a substantial decrease in viability within 36 h that was prevented mostly by silibinin. We conclude that silibinin is a potent protective compound against apoptosis and cytotoxicity caused by OTA and the investigated compounds. Full article

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Open AccessArticle

Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

by Patrycja Gazinska, Diana Herman, Cheryl Gillett, Sarah Pinder and Peter Mantle

Toxins 2012, 4(9), 643-662; https://doi.org/10.3390/toxins4090643 - 11 Sep 2012

Cited by 13 | Viewed by 7468

Abstract

Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the [...] Read more.

Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis. Full article

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Open AccessReview

Control of Ochratoxin A Production in Grapes

by María Lorena Ponsone, María Laura Chiotta, Juan Manuel Palazzini, Mariana Combina and Sofía Chulze

Toxins 2012, 4(5), 364-372; https://doi.org/10.3390/toxins4050364 - 14 May 2012

Cited by 32 | Viewed by 8074

Abstract

Ochratoxin A (OTA) is a mycotoxin commonly present in cereals, grapes, coffee, spices, and cocoa. Even though the main objective of the food and feed chain processors and distributors is to avoid the extended contamination of plant-derived foods and animal feeds with mycotoxins, [...] Read more.

Ochratoxin A (OTA) is a mycotoxin commonly present in cereals, grapes, coffee, spices, and cocoa. Even though the main objective of the food and feed chain processors and distributors is to avoid the extended contamination of plant-derived foods and animal feeds with mycotoxins, until now, complete OTA removal from foods and feedstuffs is not feasible. Prevention through pre-harvest management is the best method for controlling mycotoxin contamination. However, in the case that the contamination occurs after this stage, the hazards associated with OTA must be managed through post-harvest strategies. Due to the increasing number of fungal strains resistant to chemical fungicides and the impact of these pesticides on the environment and human health, maximum levels of chemical residues have been regulated in many products. Alternative methods are necessary to substitute or complement treatments with fungicides to control fungi under field or storage conditions. Yeasts are considered one of the most potent biocontrol agents due to their biology and non-toxic properties. Epiphytic yeasts are the major component of the microbial community on the surface of grape berries and they are evolutionarily adapted to this ecological niche. Nowadays, several yeast species included in different genera are considered as potential biocontrol agents to control both, growth of ochratoxigenic Aspergillus species and OTA accumulation. Full article

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Open AccessArticle

Dimethylarginine Dimethylaminohydrolase/Nitric Oxide Synthase Pathway in Liver and Kidney: Protective Effect of Cyanidin 3-O-β-D-Glucoside on Ochratoxin-A Toxicity

by Valeria Sorrenti, Claudia Di Giacomo, Rosaria Acquaviva, Matteo Bognanno, Ester Grilli, Nicolantonio D’Orazio and Fabio Galvano

Toxins 2012, 4(5), 353-363; https://doi.org/10.3390/toxins4050353 - 8 May 2012

Cited by 18 | Viewed by 7300

Abstract

The aim of the present study was to evaluate the effect of long-term cyanidin 3-O-β-D-glucoside (C3G) and/or Ochratoxin A (OTA)-exposure on dimethylarginine dimethylamino hydrolase/nitric oxide synthase (DDAH/NOS) pathway in rats. The experiments were performed in rats supplemented with C3G (1 g/kg [...] Read more.

The aim of the present study was to evaluate the effect of long-term cyanidin 3-O-β-D-glucoside (C3G) and/or Ochratoxin A (OTA)-exposure on dimethylarginine dimethylamino hydrolase/nitric oxide synthase (DDAH/NOS) pathway in rats. The experiments were performed in rats supplemented with C3G (1 g/kg feed), OTA (200 ppb), and OTA + C3G. After 4 weeks of daily treatment, liver and kidneys were processed for eNOS, iNOS and DDAH-1 Western blotting, nitrite levels evaluation and DDAH activity determination. Results show that OTA is able to induce iNOS both in kidney and liver, whereas OTA is able to induce eNOS and DDAH-1 overexpression and DDAH activation only in kidney, resulting in increased nitrite levels. In kidney of OTA + C3G fed rats, iNOS, eNOS and DDAH-1 expression were less pronounced compared with those observed in the OTA-treated group. Coherent with the decreased iNOS, eNOS and DDAH-1 expression a decrease in nitrite levels and DDAH activity was observed in the OTA + C3G group. Results demonstrate that C3G is able to counteract the deleterious effects of chronic consumption of OTA and also suggest a possible involvement of iNOS-eNOS-DDAH impairment in OTA nephrocarcinogenity. Full article

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Open AccessArticle

Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the SupF Gene of the Mutation Reporter Plasmid Ps189

by Steven A. Akman, Marissa Adams, Doug Case, Gyungse Park and Richard A. Manderville

Toxins 2012, 4(4), 267-280; https://doi.org/10.3390/toxins4040267 - 16 Apr 2012

Cited by 19 | Viewed by 7937

Abstract

Ochratoxin A (OTA) is a mycotoxin that enhances renal tumor formation in the outer medulla of male rat kidney. Direct DNA damage and subsequent mutagenicity may contribute to these processes. In this study we have determined whether OTA in the absence or presence [...] Read more.

Ochratoxin A (OTA) is a mycotoxin that enhances renal tumor formation in the outer medulla of male rat kidney. Direct DNA damage and subsequent mutagenicity may contribute to these processes. In this study we have determined whether OTA in the absence or presence of activated rat liver microsomes (RLM) or redox-active transition metals (Fe(III) or Cu(II)) causes promutagenic DNA damage in the supF gene of the mutation reporter plasmid pS189 replicating in human Ad293 cells. In addition, we have assessed the mutagenicity of the hydroquinone metabolite (OTHQ) of OTA in the absence or presence of cysteine without added cofactors. Our results show that oxidation of OTA, either by RLM or by transition metal ions, activates OTA to a directly genotoxic mutagen(s). The Fe(III)/OTA system was the most potent mutagen in our experimental system, causing a 32-fold increase in mutant fraction (MF) above the spontaneous control MF. The Cu(II)/OTA system caused a 9-fold increase in MF, while a 6–10-fold increase in MF was observed for OTA in the presence of RLM. The OTHQ metabolite is also mutagenic, especially in the presence of cysteine, in which a 6-fold increase in MF was observed. Our data provide further insight into OTA bioactivation that may account for its in vivo mutagenicity in male rat kidney. Full article

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Open AccessReview

Immunochemical Methods for Ochratoxin A Detection: A Review

by Eline P. Meulenberg

Toxins 2012, 4(4), 244-266; https://doi.org/10.3390/toxins4040244 - 13 Apr 2012

Cited by 120 | Viewed by 10794

Abstract

The safety of food and feed depends to a great deal on quality control. Numerous compounds and organisms may contaminate food and feed commodities and thus pose a health risk for consumers. The compound of interest in this review is ochratoxin A (OTA), [...] Read more.

The safety of food and feed depends to a great deal on quality control. Numerous compounds and organisms may contaminate food and feed commodities and thus pose a health risk for consumers. The compound of interest in this review is ochratoxin A (OTA), a secondary metabolite of the fungi Aspergillus and Penicillium. Due to its adverse health effects, detection and quantification are of utmost importance. Quality control of food and feed requires extraction and analysis, including TLC, HPLC, MS, and immunochemical methods. Each of these methods has its advantages and disadvantages. However, with regard to costs and rapidity, immunochemical methods have gained much interest in the last decade. In this review an introduction to immunochemistry and assay design will be given to elucidate the principles. Further, the application of the various formats to the detection and quantification of ochratoxin will be described, including the use of commercially available kits. Full article

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Open AccessCommunication

Sorption of Ochratoxin A from Aqueous Solutions Using β-Cyclodextrin-Polyurethane Polymer

by Michael Appell and Michael A. Jackson

Toxins 2012, 4(2), 98-109; https://doi.org/10.3390/toxins4020098 - 6 Feb 2012

Cited by 38 | Viewed by 7290

Abstract

The ability of a cyclodextrin-polyurethane polymer to remove ochratoxin A from aqueous solutions was examined by batch rebinding assays. The results from the aqueous binding studies were fit to two parameter models to gain insight into the interaction of ochratoxin A with the [...] Read more.

The ability of a cyclodextrin-polyurethane polymer to remove ochratoxin A from aqueous solutions was examined by batch rebinding assays. The results from the aqueous binding studies were fit to two parameter models to gain insight into the interaction of ochratoxin A with the nanosponge material. The ochratoxin A sorption data fit well to the heterogeneous Freundlich isotherm model. The polymer was less effective at binding ochratoxin A in high pH buffer (9.5) under conditions where ochratoxin A exists predominantly in the dianionic state. Batch rebinding assays in red wine indicate the polymer is able to remove significant levels of ochratoxin A from spiked solutions between 1–10 μg·L⁻¹. These results suggest cyclodextrin nanosponge materials are suitable to reduce levels of ochratoxin A from spiked aqueous solutions and red wine samples. Full article

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Open AccessArticle

Biocontrol of Penicillium nordicum Growth and Ochratoxin A Production by Native Yeasts of Dry Cured Ham

by Roberta Virgili, Nicoletta Simoncini, Tania Toscani, Marco Camardo Leggieri, Silvia Formenti and Paola Battilani

Toxins 2012, 4(2), 68-82; https://doi.org/10.3390/toxins4020068 - 1 Feb 2012

Cited by 63 | Viewed by 12763

Abstract

Twelve yeast strains isolated from the surface of Italian typical dry-cured hams, belonging to D. hansenii, D. maramus, C. famata, C. zeylanoides and H. burtonii species, and previously selected for their ability to grow in dry-cured ham-like substrates, were screened [...] Read more.

Twelve yeast strains isolated from the surface of Italian typical dry-cured hams, belonging to D. hansenii, D. maramus, C. famata, C. zeylanoides and H. burtonii species, and previously selected for their ability to grow in dry-cured ham-like substrates, were screened for antagonistic activity against a toxigenic strain of P. nordicum and inhibition of ochratoxin A (OTA) biosynthesis. On average, yeast inhibitory activity was lowered by increasing fungal inoculum and enhanced by NaCl presence. In the assay conditions, H. burtonii and C. zeylanoides were the most effective, both in inhibiting P. nordicum growth and OTA production. D. hansenii was the species with the lowest inhibitory activity, especially in the absence of salt. OTA production dropped from the range < LOD − 5000 ppb in P. nordicum control plates to the range < LOD − 200 ppb in yeast-added plates. OTA production increased in the presence of NaCl in P. nordicum control plates, while salt enhanced inhibition against OTA production in yeast-added plates. Full article

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Open AccessArticle

Ochratoxigenic Black Species of Aspergilli in Grape Fruits of Northern Italy Identified by an Improved PCR-RFLP Procedure

by Davide Spadaro, Subban Patharajan, Alessia Lorè, Angelo Garibaldi and Maria Lodovica Gullino

Toxins 2012, 4(2), 42-54; https://doi.org/10.3390/toxins4020042 - 30 Jan 2012

Cited by 25 | Viewed by 6955

Abstract

A collection of 356 isolates of Aspergillus spp. collected during 2006 and 2007 from grapevines in northern Italy were identified through Internal Transcribed Spacer based Restriction Fragment Length Polymorphism (ITS-RFLP) and tested for ochratoxin A (OTA) production. Restriction endonuclease digestion of the ITS [...] Read more.

A collection of 356 isolates of Aspergillus spp. collected during 2006 and 2007 from grapevines in northern Italy were identified through Internal Transcribed Spacer based Restriction Fragment Length Polymorphism (ITS-RFLP) and tested for ochratoxin A (OTA) production. Restriction endonuclease digestion of the ITS products using the endonucleases HhaI, HinfI and RsaI, distinguished five different RFLPs. From each pattern, three samples were sequenced and the nucleotide sequences showed different species corresponding to Aspergillus niger, A. carbonarius, A. tubingensis, A. japonicus and A. aculeatus. By comparing the sequences of the ITS regions, also the uniseriate species A. japonicus and A. aculeatus could be differentiated by HinfI digestion of the ITS products. Among the aspergilli, A. niger was the major species associated with grapes during 2006 (57.4%), while A. carbonarius was the major species during 2007 (46.6%). All the strains of Aspergillus were tested for their ability to produce OTA on Yeast extract sucrose medium (YES), as it was tested as an optimal substrate for the evaluation of OTA production by black aspergilli. Out of 356 isolates, 63 (17.7%) isolates produced OTA ranging from 0.05 to 3.0 µg mL⁻¹. Most of the ochratoxigenic isolates were A. carbonarius (46) in both years, but also some strains of A. tubingensis (11) and A. japonicus (6) produced lower amounts of OTA. Full article

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Open AccessReview

Ecophysiology of Aspergillus Section Nigri Species Potential Ochratoxin A Producers

by Andrea L. Astoreca, Carina E. Magnoli and Ana M. Dalcero

Toxins 2010, 2(11), 2593-2605; https://doi.org/10.3390/toxins2112593 - 29 Oct 2010

Cited by 28 | Viewed by 8980

Abstract

After aflatoxins, ochratoxin A (OTA) is the most studied mycotoxin due to the toxicological significance in human and animal diets. OTA presence has been extensively reported worldwide in the last decade in several agricultural products. The main OTA producer in tropical and temperate [...] Read more.

After aflatoxins, ochratoxin A (OTA) is the most studied mycotoxin due to the toxicological significance in human and animal diets. OTA presence has been extensively reported worldwide in the last decade in several agricultural products. The main OTA producer in tropical and temperate climates is Aspergillus carbonarius followed by species belonging to A. niger aggregate. Currently, many scientists worldwide have studied the influence of water activity and temperature for growth and biosynthesis of OTA by these species on synthetic media. This article reviews ecophysiological studies of Aspergillus section Nigri strains on synthetic media and natural substrates. The results of these investigations suggest that significant amounts of OTA can be produced in only five days and that the use of different storage practices, such as a_W and temperature levels below 0.930 and 15 °C, respectively, allow controlling fungal contamination and minimizing the OTA production in several products as peanuts, corn, dried grapes and derived products for human consumption. Full article

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Open AccessReply

Response to Comments of Peter G. Mantle

by Gary G. Schwartz, Richard A. Manderville and Annie Pfohl-Leszkowicz

Toxins 2010, 2(10), 2337-2339; https://doi.org/10.3390/toxins2102337 - 29 Sep 2010

Cited by 10 | Viewed by 8154

Abstract

The apparently high yield of testis tumors (25%) in rats exposed long-term to Ochratoxin A (OTA) is uninterpretable without data on tumor yield in unexposed rats. Conversely, our demonstration that prenatal exposure to OTA induces DNA adducts in the testes of newborn mice [...] Read more.

The apparently high yield of testis tumors (25%) in rats exposed long-term to Ochratoxin A (OTA) is uninterpretable without data on tumor yield in unexposed rats. Conversely, our demonstration that prenatal exposure to OTA induces DNA adducts in the testes of newborn mice and the absence of these adducts in the testes of mice not exposed prenatally to OTA, is evidence for the presumptive carcinogenicity of OTA in the testis. Together with recent data showing that prenatal exposure to OTA depresses expression of DMRT1, a tumor suppressor gene in the testis, our findings suggest that OTA may be a cause of testicular cancer. Full article

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Open AccessCommentary

Comments on “Ochratoxin A: In utero Exposure in Mice Induces Adducts in Testicular DNA. Toxins 2010, 2, 1428–1444”—Mis-Citation of Rat Literature to Justify a Hypothetical Role for Ochratoxin A in Testicular Cancer

by Peter G. Mantle

Toxins 2010, 2(10), 2333-2336; https://doi.org/10.3390/toxins2102333 - 29 Sep 2010

Cited by 7 | Viewed by 8559

Abstract

A manuscript in the journal recently cited experimental rat data from two manuscripts to support plausibility of a thesis that ochratoxin A might be a cause of human testicular cancer. I believe that there is no experimental evidence that ochratoxin A produces testicular [...] Read more.

A manuscript in the journal recently cited experimental rat data from two manuscripts to support plausibility of a thesis that ochratoxin A might be a cause of human testicular cancer. I believe that there is no experimental evidence that ochratoxin A produces testicular cancer in rats or mice. Full article

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Open AccessReview

Rapid Visual Tests: Fast and Reliable Detection of Ochratoxin A

by Ingrid Bazin, Elodie Nabais and Miguel Lopez-Ferber

Toxins 2010, 2(9), 2230-2241; https://doi.org/10.3390/toxins2092230 - 26 Aug 2010

Cited by 45 | Viewed by 13297

Abstract

This paper reviews the early detection strategies that have been employed for the rapid monitoring of ochratoxin A (OTA) contamination of food. OTA, a mycotoxin mainly produced by some Aspergillus and Penicillium species, is found in cereals, coffee, wine, pork and grapes. To [...] Read more.

This paper reviews the early detection strategies that have been employed for the rapid monitoring of ochratoxin A (OTA) contamination of food. OTA, a mycotoxin mainly produced by some Aspergillus and Penicillium species, is found in cereals, coffee, wine, pork and grapes. To minimize the entry of this mycotoxin into the food chain, rapid diagnostic tools are required. To this end, the potential use of lateral flow devices has also been developed. In this study, we analyze the robustness of test strips using published methods for colorimetric detection. Different test formats are discussed, and challenges in the development of lateral flow devices for on-site determination of OTA, with requirements such as robustness, speed, and cost-effectiveness, are discussed. Full article

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Open AccessArticle

Ochratoxin A Contamination of Food from Croatia

by Maja Peraica, Dubravka Flajs, Ana-Marija Domijan, Dario Ivić and Bogdan Cvjetković

Toxins 2010, 2(8), 2098-2105; https://doi.org/10.3390/toxins2082098 - 10 Aug 2010

Cited by 15 | Viewed by 10144

Abstract

Ochratoxin A (OTA) is a mycotoxin with nephrotoxic, genotoxic and carcinogenic properties produced by Penicillium and Aspergillus moulds under different climatic conditions. Humans and animals are exposed to this compound mainly via ingestion of contaminated food. In Croatia, research on mycotoxins focused on [...] Read more.

Ochratoxin A (OTA) is a mycotoxin with nephrotoxic, genotoxic and carcinogenic properties produced by Penicillium and Aspergillus moulds under different climatic conditions. Humans and animals are exposed to this compound mainly via ingestion of contaminated food. In Croatia, research on mycotoxins focused on OTA when the mycotoxin theory of endemic nephropathy (EN) was postulated. Ochratoxin A was more frequent and at higher concentration in foods from EN than those from the control regions. Subsequently, OTA concentrations were determined in some commodities intended for human consumption such as maize, wheat, beans and wine. Samples from all parts of Croatia were analyzed and OTA was found in all types of commodities. It was frequently found together with other mycotoxins (fumonisin B₁, fumonisin B₂ and zearalenone). In general, OTA concentration in foods from Croatia is low, but the frequency of positive samples shows considerable variations from year to year depending also on sampling location. Although low levels of OTA were found in a large proportion of analyzed food samples, its persistent co-occurrence with other significant mycotoxins should raise serious public health concerns as there interactions may be synergistic or additive in causing toxicity in humans and animals. There is need to establish control measures through which such contaminations in foods can be managed. Full article

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Open AccessArticle

Natural Occurrence of Ochratoxin A in Musts, Wines and Grape Vine Fruits from Grapes Harvested in Argentina

by María Lorena Ponsone, María Laura Chiotta, Mariana Combina, Adriana Torres, Patricia Knass, Ana Dalcero and Sofía Chulze

Toxins 2010, 2(8), 1984-1996; https://doi.org/10.3390/toxins2081984 - 3 Aug 2010

Cited by 23 | Viewed by 9804

Abstract

In this study, ochratoxin A (OTA) occurrence in Argentinean musts, wines and dried vine fruits was evaluated, alongside with the performance of OchraStar^TM columns for OTA extraction. In all the three matrices analyzed, the OchraStar^TMcolumns showed good performance. The analysis [...] Read more.

In this study, ochratoxin A (OTA) occurrence in Argentinean musts, wines and dried vine fruits was evaluated, alongside with the performance of OchraStar^TM columns for OTA extraction. In all the three matrices analyzed, the OchraStar^TMcolumns showed good performance. The analysis of natural occurrence of OTA in the red must and the red wine samples showed low incidence with low levels of mean OTA contamination (0.12 ng/mL and 0.37 ng/mL, respectively), while 60% of the dried vine fruit samples were contaminated with OTA, in levels ranging from 0.26 to 20.28 ng/g. Full article

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Open AccessReview

Effects of Ochratoxin A on Livestock Production

by Gianni Battacone, Anna Nudda and Giuseppe Pulina

Toxins 2010, 2(7), 1796-1824; https://doi.org/10.3390/toxins2071796 - 8 Jul 2010

Cited by 79 | Viewed by 12664

Abstract

Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain [...] Read more.

Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain to humans. The aim of this paper is to review the available literature on: (1) the frequency and degree of occurrence of OTA in different feedstuffs; (2) the toxicological effects of OTA intake on the performance of the main livestock (i.e., poultry, swine, cattle, goats and sheep); and (3) the transfer of OTA, or its metabolites, from animal feed into animal products such as milk, meat and eggs. Full article

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Open AccessReview

Chemical, Physical and Biological Approaches to Prevent Ochratoxin Induced Toxicoses in Humans and Animals

by János Varga, Sándor Kocsubé, Zsanett Péteri, Csaba Vágvölgyi and Beáta Tóth

Toxins 2010, 2(7), 1718-1750; https://doi.org/10.3390/toxins2071718 - 1 Jul 2010

Cited by 95 | Viewed by 14054

Abstract

Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard [...] Read more.

Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard to animals and humans. Several strategies have been investigated for lowering the ochratoxin content in agricultural products. These strategies can be classified into three main categories: prevention of ochratoxin contamination, decontamination or detoxification of foods contaminated with ochratoxins, and inhibition of the absorption of consumed ochratoxins in the gastrointestinal tract. This paper gives an overview of the strategies that are promising with regard to lowering the ochratoxin burden of animals and humans. Full article

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Open AccessArticle

Development and Characterization of a Monoclonal Antibody against Ochratoxin B and Its Application in ELISA

by Alexandra H. Heussner, Simon Ausländer and Daniel R. Dietrich

Toxins 2010, 2(6), 1582-1594; https://doi.org/10.3390/toxins2061582 - 21 Jun 2010

Cited by 13 | Viewed by 9106

Abstract

A monoclonal antibody specific to ochratoxin B (OTB) was employed for the development of an indirect competitive OTB-ELISA. The optimized OTB-ELISA resulted in a limit of detection (LOD) for OTB of 3 µg/L (8 nM), a limit of quantification (LOQ) of 3.7 µg/L [...] Read more.

A monoclonal antibody specific to ochratoxin B (OTB) was employed for the development of an indirect competitive OTB-ELISA. The optimized OTB-ELISA resulted in a limit of detection (LOD) for OTB of 3 µg/L (8 nM), a limit of quantification (LOQ) of 3.7 µg/L (10 nM), and a 50% inhibitory concentration (IC50) of 150 nM. Due to very low cross-reactivity to OTA (2.7%) and structurally related molecules (0%), this OTB-ELISA was found to be suitable to detect OTB with excellent precision in different matrices, i.e., beer, coffee and wine. Therefore, this OTB-ELISA will allow screening of OTB in food and feed products. Full article

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Open AccessReview

Molecularly Imprinted Polymers for Ochratoxin A Extraction and Analysis

by Jorn C. C. Yu and Edward P. C. Lai

Toxins 2010, 2(6), 1536-1553; https://doi.org/10.3390/toxins2061536 - 18 Jun 2010

Cited by 53 | Viewed by 10777

Abstract

Molecularly imprinted polymers (MIPs) are considered as polymeric materials that mimic the functionality of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, solid phase extraction, immunoassays, and sensor recognition. In this article, recent advances of MIPs for the [...] Read more.

Molecularly imprinted polymers (MIPs) are considered as polymeric materials that mimic the functionality of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, solid phase extraction, immunoassays, and sensor recognition. In this article, recent advances of MIPs for the extraction and analysis of ochratoxins are discussed. Selection of functional monomers to bind ochratoxin A (OTA) with high affinities, optimization of extraction procedures, and limitations of MIPs are compared from different reports. The most relevant examples in the literature are described to clearly show how useful these materials are. Strategies on MIP preparation and schemes of analytical methods are also reviewed in order to suggest the next step that would make better use of MIPs in the field of ochratoxin research. The review ends by outlining the remaining issues and impediments. Full article

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Open AccessArticle

Ochratoxin A: In Utero Exposure in Mice Induces Adducts in Testicular DNA

by Jamie E. Jennings-Gee, Mariana Tozlovanu, Richard Manderville, Mark Steven Miller, Annie Pfohl-Leszkowicz and Gary G. Schwartz

Toxins 2010, 2(6), 1428-1444; https://doi.org/10.3390/toxins2061428 - 11 Jun 2010

Cited by 52 | Viewed by 11362

Abstract

Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same [...] Read more.

Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same embryonic tissue, we reasoned that OTA also may cause adducts transplacentally in the testis. We tested the hypothesis that acute exposure to OTA, via food and via exposure in utero, causes adducts in testicular DNA and that these lesions are identical to those that can be produced in the kidney and testis by the consumption of OTA. Adult mice received a single dose of OTA (from 0–1,056 µg/kg) by gavage. Pregnant mice received a single i.p. injection of OTA (2.5 mg/kg) at gestation day 17. DNA adducts were determined by ³²P-postlabeling. Gavage-fed animals sacrificed after 48 hours accumulated OTA in kidney and testis and showed DNA adducts in kidney and testis. Some OTA metabolites isolated from the tissues were similar in both organs (kidney and testis). The litters of mice exposed prenatally to OTA showed no signs of overt toxicity. However, newborn and 1-month old males had DNA adducts in kidney and testis that were chromatographically similar to DNA adducts observed in the kidney and testis of gavage-fed adults. One adduct was identified previously as C8-dG-OTA adduct by LC MS/MS. No adducts were observed in males from dams not exposed to OTA. Our findings that in utero exposure to OTA causes adducts in the testicular DNA of male offspring support a possible role for OTA in testicular cancer. Full article

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Open AccessReview

«Suspects» in Etiology of Endemic Nephropathy: Aristolochic Acid versus Mycotoxins

by Stjepan Pepeljnjak and Maja Šegvić Klarić

Toxins 2010, 2(6), 1414-1427; https://doi.org/10.3390/toxins2061414 - 11 Jun 2010

Cited by 19 | Viewed by 9141

Abstract

Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs [...] Read more.

Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs nephropathy (CHN) and EN, findings of AA-DNA adducts in EN and in patients with urinary tract tumors (UTT), as well as the domination of A:T→T:A transversions in the p53 mutational spectrum of UTT patients, which corresponds with findings of such mutations in AA-treated rats. However, exposure pathways of EN residents to AA are unclear. Experimental studies attempting to deduce whether nephrotoxins OTA and CIT appear at higher frequencies or levels (or both) in the food and blood or urine of EN residents support the mycotoxin theory. Also, some molecular studies revealed the presence of OTA-DNA adducts in the renal tissue of EN and UTT patients. In this review, data supporting or arguing against AA and mycotoxin theory are presented and discussed. Full article

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Open AccessReview

Molecular Mechanism of Ochratoxin A Transport in the Kidney

by Naohiko Anzai, Promsuk Jutabha and Hitoshi Endou

Toxins 2010, 2(6), 1381-1398; https://doi.org/10.3390/toxins2061381 - 9 Jun 2010

Cited by 62 | Viewed by 12704

Abstract

The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic [...] Read more.

The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic anion transport system. Recently, several families of multispecific organic anion transporters have been identified: organic anion transporters (OATs), organic anion-transporting polypeptides (OATPs), oligopeptide transporters (PEPTs), and ATP-binding cassette (ABC) transporters, such as MRP2 and BCRP. These renal transporters mediate the transmembrane transport of OTA and play a pivotal role in the development of OTA-induced nephrotoxicity. Full article

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Open AccessArticle

Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α

by Lauy Al-Anati, Ebtisam Essid, Ulla Stenius, Knut Beuerlein, Klaus Schuh and Ernst Petzinger

Toxins 2010, 2(6), 1279-1299; https://doi.org/10.3390/toxins2061279 - 1 Jun 2010

Cited by 14 | Viewed by 11716

Abstract

The release of tumor necrosis factor α (TNF-α) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-α release agent. Cells were exposed either to 0, 2.5 or 12.5 [...] Read more.

The release of tumor necrosis factor α (TNF-α) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-α release agent. Cells were exposed either to 0, 2.5 or 12.5 µmol/L OTA, or to 0.1 µg/mL LPS, for up to 24 h. OTA at 2.5 µmol/L and LPS at 0.1 µg/mL were not toxic to the tested cells as indicated by viability markers. TNF-a was detected in the incubated cell medium of rat Kupffer cells, peritoneal rat macrophages, and the mouse monocyte macrophage cell line J774A.1: TNF-a concentrations were 1,000 pg/mL, 1,560 pg/mL, and 650 pg/mL, respectively, for 2.5 µmol/L OTA exposure and 3,000 pg/mL, 2,600 pg/mL, and 2,115 pg/mL, respectively, for LPS exposure. Rat liver sinusoidal endothelial cells, rat hepatocytes, human HepG2 cells, and mouse L929 cells lacked any cytokine response to OTA, but showed a significant release of TNF-a after LPS exposure, with the exception of HepG2 cells. In non-responsive cell lines, OTA lacked both any activation of NF-κB or the translocation of activated NF-κB to the cell nucleus, i.e., in mouse L929 cells. In J774A.1 cells, OTA mediated TNF-a release via the pRaf/MEK 1/2–NF-κB and p38-NF-κB pathways, whereas LPS used pRaf/MEK 1/2-NF-κB, but not p38-NF-κB pathways. In contrast, in L929 cells, LPS used other pathways to activate NF-κB. Our data indicate that only macrophages and macrophage derived cells respond to OTA and are considered as sources for TNF-a release upon OTA exposure. Full article

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Open AccessArticle

Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

by Eleonora Fusi, Raffaella Rebucci, Chiara Pecorini, Anna Campagnoli, Luciano Pinotti, Francesca Saccone, Federica Cheli, Stig Purup, Kristen Sejrsen and Antonella Baldi

Toxins 2010, 2(6), 1265-1278; https://doi.org/10.3390/toxins2061265 - 1 Jun 2010

Cited by 30 | Viewed by 10964

Abstract

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in [...] Read more.

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity. Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P < 0.01) reduced OTA cytotoxicity, lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that α-tocopherol supplementation may counteract short-term OTA toxicity, supporting its defensive role in the cell membrane. Full article

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Open AccessReview

Ochratoxin A in Portugal: A Review to Assess Human Exposure

by Sofia C. Duarte, Angelina Pena and Celeste M. Lino

Toxins 2010, 2(6), 1225-1249; https://doi.org/10.3390/toxins2061225 - 1 Jun 2010

Cited by 31 | Viewed by 10756

Abstract

In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA), one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on [...] Read more.

In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA), one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on OTA research, a summary of the available data on OTA occurrence in food (cereals, bread, wine, meat) and biological fluids (blood, urine) is made. With this data, an estimation of intake is made to ascertain and update the risk exposure estimation of the Portuguese population, in comparison to previous studies and other populations. Full article

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Open AccessReview

Ochratoxin A in Moroccan Foods: Occurrence and Legislation

by Abdellah Zinedine

Toxins 2010, 2(5), 1121-1133; https://doi.org/10.3390/toxins2051121 - 14 May 2010

Cited by 22 | Viewed by 10650

Abstract

Ochratoxin A (OTA) is secondary metabolite naturally produced in food and feed by toxigenic fungi, especially some Aspergillus species and Penicillium verucosum. OTA is one of the most studied mycotoxins and is of great interest due to its toxic effects on human [...] Read more.

Ochratoxin A (OTA) is secondary metabolite naturally produced in food and feed by toxigenic fungi, especially some Aspergillus species and Penicillium verucosum. OTA is one of the most studied mycotoxins and is of great interest due to its toxic effects on human and animals. OTA is produced in different food and feed matrices and contaminates a large range of base foods including cereals and derivatives, spices, dried fruits, wine and coffee, etc. Morocco, a North African country, has a climate characterized by high humidity and temperature, which probably favors the growth of molds. This contribution gives an overview of principal investigations about the presence of OTA in foods available in Morocco. Due to its toxicity, OTA presence is increasingly regulated worldwide, especially in countries of the European Union. However, up until now, no regulation limits were in force in Morocco, probably due to the ignorance of the health and economic problems resulting from OTA contamination. Finally, recommendations and future research directions are given required to assess the situation completely. Full article

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Open AccessReview

Ochratoxin A Producing Species in the Genus Penicillium

by Francisco Javier Cabañes, Maria Rosa Bragulat and Gemma Castellá

Toxins 2010, 2(5), 1111-1120; https://doi.org/10.3390/toxins2051111 - 14 May 2010

Cited by 92 | Viewed by 14576

Abstract

Ochratoxin A (OTA) producing fungi are members of the genera Aspergillus and Penicillium. Nowadays, there are about 20 species accepted as OTA producers, which are distributed in three phylogenetically related but distinct groups of aspergilli of the subgenus Circumdati and only in [...] Read more.

Ochratoxin A (OTA) producing fungi are members of the genera Aspergillus and Penicillium. Nowadays, there are about 20 species accepted as OTA producers, which are distributed in three phylogenetically related but distinct groups of aspergilli of the subgenus Circumdati and only in two species of the subgenus Penicillium. At the moment, P. verrucosum and P. nordicum are the only OTA producing species accepted in the genus Penicillium. However, during the last century, OTA producers in this genus were classified as P. viridicatum for many years. At present, only some OTA producing species are known to be a potential source of OTA contamination of cereals and certain common foods and beverages such as bread, beer, coffee, dried fruits, grape juice and wine among others. Penicillium verrucosum is the major producer of OTA in cereals such as wheat and barley in temperate and cold climates. Penicillium verrucosum and P. nordicum can be recovered from some dry-cured meat products and some cheeses. Full article

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Open AccessArticle

Pathological Outcomes in Kidney and Brain in Male Fischer Rats Given Dietary Ochratoxin A, Commencing at One Year of Age

by Peter G. Mantle and Christopher C. Nolan

Toxins 2010, 2(5), 1100-1110; https://doi.org/10.3390/toxins2051100 - 13 May 2010

Cited by 19 | Viewed by 11507

Abstract

Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100–250 µg/kg body weight). Reasons for the long latency [...] Read more.

Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100–250 µg/kg body weight). Reasons for the long latency are unclear, as is whether there would be a similar carcinogenic response if toxin exposure started at one year of age. Therefore, 24 male Fischer rats were given 100 µg ochratoxin A as a daily dietary contaminant for 35 weeks from age 50 weeks. Plasma ochratoxin A concentration reached a maximum value of ~8 µg/mL within one month of starting the toxin regimen. No renal carcinomas occurred. Four renal adenomas, two of which were only microscopic, were found among the six rats surviving for 110 weeks. The findings raise new questions about a difference between young adults and mature adults in sensitivity of male rats to the ochratoxin A-induced DNA damage necessary for renal carcinogenesis. A pilot histological study of perfuse-fixed brains of the toxin-treated rats showed no gross abnormalities, correlating with the consistent absence of behavioral or neurological disorders from chronic ochratoxin A exposure regimens in the range 100–250 µg/kg/day during the second half of life. Reasoned questioning concerning ochratoxin A as a neurotoxic mycotoxin is made. Full article

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461 KiB

Open AccessReview

Biodegradation of Ochratoxin A for Food and Feed Decontamination

by Luís Abrunhosa, Robert R.M. Paterson and Armando Venâncio

Toxins 2010, 2(5), 1078-1099; https://doi.org/10.3390/toxins2051078 - 13 May 2010

Cited by 184 | Viewed by 16757

Abstract

Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus [...] Read more.

Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus and Penicillium that can be found in a wide variety of agricultural products, which makes the presence of OTA in these products common. Many countries have statutory limits for OTA, and concentrations need to be reduced to as low as technologically possible in food and feed. The most important measures to be taken to control OTA are preventive in order to avoid fungal growth and OTA production. However, these measures are difficult to implement in all cases with the consequence of OTA remaining in agricultural commodities. Remediation processes are often used to eliminate, reduce or avoid the toxic effects of OTA. Biological methods have been considered increasingly as an alternative to physical and chemical treatments. However, examples of practical applications are infrequent. This review will focus on the (i) known microorganisms and enzymes that are able to biodegrade OTA; (ii) mode of action of biodegradation and (iii) current applications. A critical discussion about the technical applicability of these strategies is presented. Full article

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223 KiB

Open AccessReview

Ochratoxins in Feed, a Risk for Animal and Human Health: Control Strategies

by Muzaffer Denli and Jose F. Perez

Toxins 2010, 2(5), 1065-1077; https://doi.org/10.3390/toxins2051065 - 13 May 2010

Cited by 73 | Viewed by 11212

Abstract

Ochratoxin A (OTA) has been shown to be a potent nephrotoxic, hepatotoxic, and teratogenic compound. In farm animals, the intake of feed contaminated with OTA affects animal health and productivity, and may result in the presence of OTA in the animal products. Strategies [...] Read more.

Ochratoxin A (OTA) has been shown to be a potent nephrotoxic, hepatotoxic, and teratogenic compound. In farm animals, the intake of feed contaminated with OTA affects animal health and productivity, and may result in the presence of OTA in the animal products. Strategies for the control of OTA in food products require early identification and elimination of contaminated commodities from the food chain. However, current analytical protocols may fail to identify contaminated products, especially in animal feed. The present paper discusses the impact of OTA on human and animal health, with special emphasis on the potential risks of OTA residue in animal products, and control strategies applied in the feed industry. Full article

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Open AccessArticle

Occurrence of Ochratoxin A in Southern Spanish Generous Wines under the Denomination of Origin “Jerez-Xérès-Sherry and ‘Manzanilla’ Sanlúcar de Barrameda”

by Mª Teresa Murillo-Arbizu, Susana Amézqueta, Elena González-Peñas and Adela López De Cerain

Toxins 2010, 2(5), 1054-1064; https://doi.org/10.3390/toxins2051054 - 12 May 2010

Cited by 14 | Viewed by 10051

Abstract

The mycotoxin ochratoxin A (OTA) has toxic effects in animals; the most relevant of them is nephrotoxicity. OTA has also been classified as a possible carcinogen for humans (group 2B) by the International Agency for Research on Cancer (IARC). Therefore, exposure to OTA [...] Read more.

The mycotoxin ochratoxin A (OTA) has toxic effects in animals; the most relevant of them is nephrotoxicity. OTA has also been classified as a possible carcinogen for humans (group 2B) by the International Agency for Research on Cancer (IARC). Therefore, exposure to OTA through contaminated food can represent health impairment to humans. The maximum permitted level for this mycotoxin in wine is 2.0 mg/L. The presence of OTA in Spanish wines produced using the traditional methods under the Denomination of Origin “Jerez-Xérès-Sherry and manzanilla Sanlúcar de Barrameda” was evaluated by a High performance Liquid Chromatography method with fluorescence detection and immunoaffinity column purification. A recovery of 95.4% and a limit of detection and quantification of 0.009 mg/L and 0.02 mg/L respectively, were achieved. In manzanilla, fino, amontillado and oloroso wine, the mean OTA values were 0.042, 0.044, 0.144, and 0.319 mg/L, respectively. These levels are not different from other data given in the reference literature on white wines, although fino and manzanilla wines have very low OTA levels. Full article

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Open AccessArticle

Occurrence of Black Aspergilli and Ochratoxin A on Grapes in Italy

by Gianluca Lucchetta, Irene Bazzo, Gianluca Dal Cortivo, Lisa Stringher, Diego Bellotto, Michele Borgo and Elisa Angelini

Toxins 2010, 2(4), 840-855; https://doi.org/10.3390/toxins2040840 - 21 Apr 2010

Cited by 33 | Viewed by 10108

Abstract

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered [...] Read more.

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered the main source of OTA in grapes, was mostly found in Southern Italy. The year and the environment had an important influence on the development of the black Aspergillus populations. Testing with ELISA showed OTA to be present in about 30% of the samples. Samples from Southern Italy showed the highest occurrence (45%) and also the highest OTA concentration, sometimes higher than 2 mg/L. The values decreased progressively the further North the samples were taken. Full article

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Open AccessReview

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

by Muhammad Mobashar, Jürgen Hummel, Ralf Blank and Karl-Heinz Südekum

Toxins 2010, 2(4), 809-839; https://doi.org/10.3390/toxins204809 - 21 Apr 2010

Cited by 48 | Viewed by 12209

Abstract

Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical [...] Read more.

Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical methods, probably due to some rumen bypass at proportions of estimated 2–6.5% of dosage (maximum 10%). High concentrate proportions and high feeding levels are dietary factors promoting the likeliness of systemic occurrence due to factors like shifts in microbial population and higher contamination potential. Among risk scenarios for ruminants, chronic intoxication represents the most relevant. Full article

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Open AccessArticle

Ochratoxin A and β2-Microglobulin in BEN Patients and Controls

by Pavlina Yordanova, Karmaus Wilfried, Svetla Tsolova and Plamen Dimitrov

Toxins 2010, 2(4), 780-792; https://doi.org/10.3390/toxins2040780 - 20 Apr 2010

Cited by 10 | Viewed by 9972

Abstract

Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine [...] Read more.

Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine β2-microglobulin, a marker of impaired ability of the kidneys to re-absorb, is related to OTA. BEN patients had significantly higher OTA serum levels. Within the offspring, OTA was significantly related to higher β2-microglobulin excretion. OTA (2005/2006) was related to a higher incidence of BEN after 2008, providing further evidence that OTA is a risk factor for BEN. Full article

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Open AccessReview

Ochratoxins—Food Contaminants: Impact on Human Health

by Lalini Reddy and Kanti Bhoola

Toxins 2010, 2(4), 771-779; https://doi.org/10.3390/toxins2040771 - 20 Apr 2010

Cited by 120 | Viewed by 25330

Abstract

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus [...] Read more.

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between endemic nephrotoxicity in humans to their daily household intake of OTA. OTA has been reported to contribute to endemic nephrotoxicity and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in kidneys. OTA may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of endemic nephrotoxicity has been mostly reported in northeast Europe since the early fifties. Recent studies however have warned that OTA and other toxins, such as aristolochic acid, show very similar renal pathology. There is thus the need for thorough co-occurrence studies on toxin incidence. Full article

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Open AccessArticle

Ochratoxin A and Aflatoxins in Liquorice Products

by Amedeo Pietri, Silvia Rastelli and Terenzio Bertuzzi

Toxins 2010, 2(4), 758-770; https://doi.org/10.3390/toxins2040758 - 20 Apr 2010

Cited by 30 | Viewed by 10031

Abstract

The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. [...] Read more.

The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. After extraction and purification through an immunoaffinity column, OTA and AFs were analysed using both HPLC-FLD and HPLC-MS/MS. OTA occurred in all samples of dried liquorice extract and in 61% of samples of liquorice confectionery, showing very high values for the former (mean 89.6 µg kg^-1, maximum value 990.1 µg kg^-1), and relatively low levels for the latter (mean 0.96 µg kg^-1, maximum value 8.3 µg kg^-1). The contribution of dried liquorice extract to OTA intake appears to be non-negligible for children, who are potentially high consumers. AF contamination resulted very low: AFB₁ was detected only in 15.8% of samples (maximum value 7.7 µg kg^-1, mean 0.38 and 0.41 µg kg^-1 for dried liquorice extract and liquorice confectionery, respectively); the other AFs were not detected. To our knowledge, it is the first time that AFB₁ has been detected in liquorice extract samples. Full article

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Open AccessArticle

Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Chicks

by Stoycho D. Stoev

Toxins 2010, 2(4), 649-664; https://doi.org/10.3390/toxins2040649 - 12 Apr 2010

Cited by 69 | Viewed by 11866

Abstract

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm [...] Read more.

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver. Full article

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Open AccessArticle

Oncological Outcomes in Rats Given Nephrocarcinogenic Exposure to Dietary Ochratoxin A, Followed by the Tumour Promoter Sodium Barbital for Life: A Pilot Study

by Peter G. Mantle, Miloslav Dobrota, Cheryl E. Gillett, Edward W. Odell and Sarah E. Pinder

Toxins 2010, 2(4), 552-571; https://doi.org/10.3390/toxins2040552 - 31 Mar 2010

Cited by 9 | Viewed by 9686

Abstract

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young [...] Read more.

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours. Full article

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Open AccessReview

Ochratoxin A: General Overview and Actual Molecular Status

by André El Khoury and Ali Atoui

Toxins 2010, 2(4), 461-493; https://doi.org/10.3390/toxins2040461 - 29 Mar 2010

Cited by 356 | Viewed by 26370

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show [...] Read more.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs. Full article

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Open AccessArticle

A Pilot Study of Nuclear Instability in Archived Renal and Upper Urinary Tract Tumours with Putative Ochratoxin Aetiology

by Peter G. Mantle, Cyrille Amerasinghe, Amy L. Brown, Diana Herman, Thomas Horn, Thoger Krogh, Edward W. Odell, Tomas Rosenbaum and Calin A. Tatu

Toxins 2010, 2(3), 326-340; https://doi.org/10.3390/toxins2030326 - 9 Mar 2010

Cited by 4 | Viewed by 11270

Abstract

DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, [...] Read more.

DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, and hyperdiploid metastasis was within the lower ploidy range for typical renal cell carcinoma. Three Balkan primary tumours showed extensive aneuploidy indicating marked nuclear instability, similar to model rat renal carcinoma caused by ochratoxin A. In contrast, much less nuclear instability in the putative occupational ochratoxicosis case fitted poorly with the ochratoxin A model. Full article

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