Toxins

2023

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13 pages, 1805 KiB

Open AccessArticle

Ameliorative Effects of Luteolin and Activated Charcoal on Growth Performance, Immunity Function, and Antioxidant Capacity in Broiler Chickens Exposed to Deoxynivalenol

by Mubashar Hassan, Yanan Wang, Shahid Ali Rajput, Aftab Shaukat, Ping Yang, Muhammad Zahid Farooq, Qianhui Cheng, Mehboob Ali, Xiaomei Mi, Yu An and Desheng Qi

Toxins 2023, 15(8), 478; https://doi.org/10.3390/toxins15080478 - 26 Jul 2023

Cited by 9 | Viewed by 2062

Abstract

Deoxynivalenol (DON, Vomitoxin) is a threatening mycotoxin that mainly produces oxidative stress and leads to hepatotoxicity in poultry. Antioxidant dietary supplements dramatically boost immunity, safeguarding animals from DON poisoning. Luteolin (LUT) is an active plant-derived compound that poses influential antioxidants. This study explored [...] Read more.

Deoxynivalenol (DON, Vomitoxin) is a threatening mycotoxin that mainly produces oxidative stress and leads to hepatotoxicity in poultry. Antioxidant dietary supplements dramatically boost immunity, safeguarding animals from DON poisoning. Luteolin (LUT) is an active plant-derived compound that poses influential antioxidants. This study explored the effectiveness of LUT in combination with activated charcoal (AC) in detoxifying DON in broilers. The 180 one-day broiler chickens were allocated into five different groups having six replicates in each group, provided with ad libitum feed during the trial period (28 days) as follows: in the control group, basal diet (feed with no supplementation of LUT, AC or DON); in group 2, a basal diet added with 10 mg/kg DON from contaminated culture (DON); in group 3, a basal diet augmented by 350 mg/kg LUT and DON 10 mg/kg (DON + LUT); in group 4, a basal diet supplemented by DON 10 mg/kg + AC 200 mg/kg (DON + AC); and in group 5, a basal diet supplemented by 10 mg/kg DON + 350 mg/kg LUT + 200 mg/kg AC (DON + LUT + AC). Concerning the control group, the DON-treated broilers demonstrated a significant decrease in growth performance (p < 0.05) and serum immunoglobulin (p < 0.05) contents, negatively changing the serum biochemical contents and enzymatic activities and an increase in histopathological liver lesions. Furthermore, DON substantially increased (p < 0.05) malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum and liver. The intake of AC and LUT to the DON-contaminated diet decreased DON residue in the liver and potentially reduced the adverse effects of DON. Considering the results, supplementation of LUT with mycotoxin adsorbent has protective effects against mycotoxicosis caused by DON. It could be helpful for the development of novel treatments to combat liver diseases in poultry birds. Our findings may provide important information for applying LUT and AC in poultry production. Full article

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2022

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16 pages, 2908 KiB

Open AccessArticle

Effect of the Combined Compound Probiotics with Glycyrrhinic Acid on Alleviating Cytotoxicity of IPEC-J2 Cells Induced by Multi-Mycotoxins

by Lijun Wang, Xiaomin Wang, Juan Chang, Ping Wang, Chaoqi Liu, Lin Yuan, Qingqiang Yin, Qun Zhu and Fushan Lu

Toxins 2022, 14(10), 670; https://doi.org/10.3390/toxins14100670 - 27 Sep 2022

Cited by 9 | Viewed by 2397

Abstract

Aflatoxins B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEA) are the three most prevalent mycotoxins, whose contamination of food and feed is a severe worldwide problem. In order to alleviate the toxic effects of multi-mycotoxins (AFB1 + DON + ZEA, ADZ) on inflammation and [...] Read more.

Aflatoxins B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEA) are the three most prevalent mycotoxins, whose contamination of food and feed is a severe worldwide problem. In order to alleviate the toxic effects of multi-mycotoxins (AFB1 + DON + ZEA, ADZ) on inflammation and apoptosis in swine jejunal epithelial cells (IPEC-J2), three species of probiotics (Bacillus subtilis, Saccharomyces cerevisiae and Pseudomonas lactis at 1 × 10⁵ CFU/mL, respectively) were mixed together to make compound probiotics (CP), which were further combined with 400 μg/mL of glycyrrhinic acid (GA) to make bioactive materials (CGA). The experiment was divided into four groups, i.e., the control, ADZ, CGA and ADZ + CGA groups. The results showed that ADZ decreased cell viability and induced cytotoxicity, while CGA addition could alleviate ADZ-induced cytotoxicity. Moreover, the mRNA expressions of IL-8, TNF-α, NF-Κb, Bcl-2, Caspase-3, ZO-1, Occludin, Claudin-1 and ASCT2 genes, and protein expressions of TNF-α and Claudin-1 were significantly upregulated in ADZ group; while the mRNA abundances of IL-8, TNF-α, NF-Κb, Caspase-3, ASCT2 genes, and protein expressions of TNF-α and Claudin-1 were significantly downregulated in the ADZ + CGA group. In addition, the protein expressions of COX-2, ZO-1, and ASCT2 were significantly downregulated in the ADZ group, compared with the control group; whereas CGA co-incubation with ADZ could increase these protein expressions to recover to normal levels. This study indicated that CGA could alleviate cytotoxicity, apoptosis and inflammation in ADZ-induced IPEC-J2 cells and protect intestinal cell integrity from ADZ damages. Full article

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2021

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20 pages, 4042 KiB

Open AccessArticle

In Vitro Analysis of Deoxynivalenol Influence on Steroidogenesis in Prostate

by Kinga Anna Urbanek, Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kamila Domińska, Agata Sakowicz and Agnieszka Wanda Piastowska-Ciesielska

Toxins 2021, 13(10), 685; https://doi.org/10.3390/toxins13100685 - 26 Sep 2021

Cited by 6 | Viewed by 2658

Abstract

Deoxynivalenol (DON) is a type-B trichothecene mycotoxin produced by Fusarium species, reported to be the most common mycotoxin present in food and feed products. DON is known to affect the production of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in male [...] Read more.

Deoxynivalenol (DON) is a type-B trichothecene mycotoxin produced by Fusarium species, reported to be the most common mycotoxin present in food and feed products. DON is known to affect the production of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in male rats, consequently affecting reproductive endpoints. Our previous study showed that DON induces oxidative stress in prostate cancer (PCa) cells, however the effect of DON on the intratumor steroidogenesis in PCa and normal prostate cells was not investigated. In this study human normal (PNT1A) and prostate cancer cell lines with different hormonal sensitivity (PC-3, DU-145, LNCaP) were exposed to DON treatment alone or in combination with dehydroepiandrosterone (DHEA) for 48 h. The results of the study demonstrated that exposure to DON alone or in combination with DHEA had a stimulatory effect on the release of estradiol and testosterone and also affected progesterone secretion. Moreover, significant changes were observed in the expression of genes related to steroidogenesis. Taken together, these results indicate that DON might affect the process of steroidogenesis in the prostate, demonstrating potential reproductive effects in humans. Full article

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2020

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16 pages, 1868 KiB

Open AccessArticle

Occurrence and Probabilistic Risk Assessment of Fumonisin B1, Fumonisin B2 and Deoxynivalenol in Nixtamalized Maize in Mexico City

by Ixchel Gilbert-Sandoval, Sebastiaan Wesseling and Ivonne M. C. M. Rietjens

Toxins 2020, 12(10), 644; https://doi.org/10.3390/toxins12100644 - 6 Oct 2020

Cited by 13 | Viewed by 3965

Abstract

Fumonisins (FB1+FB2) and deoxynivalenol (DON) are mycotoxins produced by Fusarium species that might be present in maize and maize products. Knowledge on their occurrence in nixtamalized maize from Mexico together with an accompanying risk assessment are scarce, while nixtamalized maize is an important [...] Read more.

Fumonisins (FB1+FB2) and deoxynivalenol (DON) are mycotoxins produced by Fusarium species that might be present in maize and maize products. Knowledge on their occurrence in nixtamalized maize from Mexico together with an accompanying risk assessment are scarce, while nixtamalized maize is an important food in Mexico. This study presents the occurrence of FB1 + FB2 and DON in nixtamalized maize samples collected in Mexico City and analyses their distribution and resulting estimated daily intake for Mexican consumers by a probabilistic approach using a two-dimensional Monte-Carlo simulation. The results obtained reveal that for FB1 + FB2, 47% of the Mexican men and 30% of the Mexican women might exceed the provisional tolerable daily intake (PMTDI) of 2 µg/kg bw/day for fumonisins and for DON, 9% of men and 5% of women would be exceeding the PMTDI of 1 µg/kg bw/day, corresponding to the high consumers. The results raise a flag for risk managers in Mexico, to consider regulations and interventions that lower mycotoxin levels in nixtamalized maize for human consumption. Full article

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2019

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23 pages, 5004 KiB

Open AccessArticle

Fusarium Mycotoxins Disrupt the Barrier and Induce IL-6 Release in a Human Placental Epithelium Cell Line

by Negisa Seyed Toutounchi, Astrid Hogenkamp, Soheil Varasteh, Belinda van’t Land, Johan Garssen, Aletta D. Kraneveld, Gert Folkerts and Saskia Braber

Toxins 2019, 11(11), 665; https://doi.org/10.3390/toxins11110665 - 14 Nov 2019

Cited by 10 | Viewed by 4079

Abstract

Deoxynivalenol, T-2 toxin, and zearalenone, major Fusarium mycotoxins, contaminate human food on a global level. Exposure to these mycotoxins during pregnancy can lead to abnormalities in neonatal development. Therefore, the aim of this study was to investigate the effects of Fusarium mycotoxins on [...] Read more.

Deoxynivalenol, T-2 toxin, and zearalenone, major Fusarium mycotoxins, contaminate human food on a global level. Exposure to these mycotoxins during pregnancy can lead to abnormalities in neonatal development. Therefore, the aim of this study was to investigate the effects of Fusarium mycotoxins on human placental epithelial cells. As an in vitro model of placental barrier, BeWo cells were exposed to different concentrations of deoxynivalenol, zearalenone or T-2 toxin. Cytotoxicity, effects on barrier integrity, paracellular permeability along with mRNA and protein expression and localization of junctional proteins after exposure were evaluated. Induction of proinflammatory responses was determined by measuring cytokine production. Increasing mycotoxin concentrations affect BeWo cell viability, and T-2 toxin was more toxic compared to other mycotoxins. Deoxynivalenol and T-2 toxin caused significant barrier disruption, altered protein and mRNA expression of junctional proteins, and induced irregular cellular distribution. Although the effects of zearalenone on barrier integrity were less prominent, all tested mycotoxins were able to induce inflammation as measured by IL-6 release. Overall, Fusarium mycotoxins disrupt the barrier of BeWo cells by altering the expression and structure of junctional proteins and trigger proinflammatory responses. These changes in placental barrier may disturb the maternal–fetal interaction and adversely affect fetal development. Full article

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18 pages, 4543 KiB

Open AccessEditor’s ChoiceArticle

Investigation of Zearalenone Adsorption and Biotransformation by Microorganisms Cultured under Cellular Stress Conditions

by Agnieszka Rogowska, Paweł Pomastowski, Justyna Walczak, Viorica Railean-Plugaru, Joanna Rudnicka and Bogusław Buszewski

Toxins 2019, 11(8), 463; https://doi.org/10.3390/toxins11080463 - 7 Aug 2019

Cited by 26 | Viewed by 4445

Abstract

The zearalenone binding and metabolization ability of probiotic microorganisms, such as lactic acid bacteria, Lactobacillus paracasei, Lactococcus lactis, and yeast Saccharomyces cerevisiae, isolated from food products, were examined. Moreover, the influence of cellular stress (induced by silver nanoparticles) and lyophilization on the [...] Read more.

The zearalenone binding and metabolization ability of probiotic microorganisms, such as lactic acid bacteria, Lactobacillus paracasei, Lactococcus lactis, and yeast Saccharomyces cerevisiae, isolated from food products, were examined. Moreover, the influence of cellular stress (induced by silver nanoparticles) and lyophilization on the effectiveness of tested microorganisms was also investigated. The concentration of zearalenone after a certain time of incubation with microorganisms was determined using high-performance liquid chromatography. The maximum sorption effectiveness for L. paracasei, L. lactis, and S. cerevisiae cultured in non-stress conditions was 53.3, 41.0, and 36.5%, respectively. At the same time for the same microorganisms cultured at cellular stress conditions, the maximum sorption effectiveness was improved to 55.3, 47.4, and 57.0%, respectively. Also, the effect of culture conditions on the morphology of the cells and its metabolism was examined using microscopic technique and matrix-assisted laser desorption ionization-time of flight mass spectrometry, respectively. Full article

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2 pages, 237 KiB

Open AccessCorrection

Correction: Pestka, J.J., et al. Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse. Toxins 2017, 9, 240

by James J. Pestka, Erica S. Clark, Heidi E. Schwartz-Zimmermann and Franz Berthiller

Toxins 2019, 11(5), 238; https://doi.org/10.3390/toxins11050238 - 26 Apr 2019

Viewed by 3254

Abstract

The authors wish to make the following corrections to their paper [...] Full article

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16 pages, 1771 KiB

Open AccessEditor’s ChoiceArticle

Contamination of Wheat Cultivated in Various Regions of Poland during 2017 and 2018 Agricultural Seasons with Selected Trichothecenes and Their Modified Forms

by Marcin Bryła, Edyta Ksieniewicz-Woźniak, Tomoya Yoshinari, Agnieszka Waśkiewicz and Krystyna Szymczyk

Toxins 2019, 11(2), 88; https://doi.org/10.3390/toxins11020088 - 1 Feb 2019

Cited by 18 | Viewed by 3923

Abstract

Cross-interaction of antibodies within the immunoaffinity columns used in this study facilitated the simultaneous determination of nivalenol (NIV), deoxynivalenol (DON), their glucoside derivatives (NIV-3G, DON-3G), and 3-acetyl-deoxynivalenol (3-AcDON) in wheat grain harvested in various regions of Poland. In Poland, 2018 was a warm, [...] Read more.

Cross-interaction of antibodies within the immunoaffinity columns used in this study facilitated the simultaneous determination of nivalenol (NIV), deoxynivalenol (DON), their glucoside derivatives (NIV-3G, DON-3G), and 3-acetyl-deoxynivalenol (3-AcDON) in wheat grain harvested in various regions of Poland. In Poland, 2018 was a warm, dry agricultural season, and hence, was relatively less favourable for cereal cultivation than 2017. Data on the natural occurrence of NIV-3G in wheat grain are among the first published in the literature. DON was the most frequently found mycotoxin in the tested samples; the percentage occurrence of DON-positive samples was 92% in 2017 and 61% in 2018. Moreover, DON concentrations were generally higher in 2017 samples (5.2–1670.7 µg/kg) than those in 2018 samples (range 5.0–461.7 µg/kg). A similar pattern was found for DON-3G. However, no statistically significant differences between the samples from the two agricultural seasons were observed for the other three mycotoxins that were analysed, and their concentrations were generally considerably lower. DON was strongly correlated with DON-3G (correlation coefficient r = 0.9558), while NIV was strongly correlated with NIV-3G (r = 0.9442). The percentage occurrence of NIV-3G- and DON-3G-positive samples was 14% in 2017 and 49% in 2018. The NIV-3G/NIV ratio was 5.9–35.7%, while the DON-3G/DON ratio range was 3.2–53.6%. In 2018, wheat samples from Southern Poland exhibited statistically significantly higher levels of DON than those from Northern Poland. The dry and hot summer of 2018 not only reduced wheat yields, but also limited development of Fusarium spp. Therefore, grain harvested that year was generally contaminated with relatively low levels of mycotoxins. Lower levels of DON were also accompanied by lesser amounts of DON-derivatives. Full article

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2018

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16 pages, 1412 KiB

Open AccessArticle

Relationship between Fusarium Head Blight, Kernel Damage, Concentration of Fusarium Biomass, and Fusarium Toxins in Grain of Winter Wheat Inoculated with Fusarium culmorum

by Tomasz Góral, Halina Wiśniewska, Piotr Ochodzki, Linda Kærgaard Nielsen, Dorota Walentyn-Góral and Łukasz Stępień

Toxins 2019, 11(1), 2; https://doi.org/10.3390/toxins11010002 - 21 Dec 2018

Cited by 37 | Viewed by 4847

Abstract

Winter wheat lines were evaluated for their reaction to Fusarium head blight (FHB) after inoculation with Fusarium culmorum in two field experiments. A mixture of two F. culmorum chemotypes was applied (3ADON—deoxynivalenol producing, NIV—nivalenol producing). Different types of resistance were evaluated, including head [...] Read more.

Winter wheat lines were evaluated for their reaction to Fusarium head blight (FHB) after inoculation with Fusarium culmorum in two field experiments. A mixture of two F. culmorum chemotypes was applied (3ADON—deoxynivalenol producing, NIV—nivalenol producing). Different types of resistance were evaluated, including head infection, kernel damage, Fusarium biomass content and trichothecenes B (deoxynivalenol (DON), and nivalenol (NIV)) accumulation in grain. The aim of the study was to find relationships between different types of resistance. Head infection (FHB index) and Fusarium damaged kernels (FDK) were visually scored. Fusarium biomass was analysed using real-time PCR. Trichothecenes B accumulation was analysed using gas chromatography. Wheat lines differ in their reaction to inoculation for all parameters describing FHB resistance. We found a wide variability of FHB indexes, FDK, and Fusarium biomass content. Both toxins were present. DON content was about 60% higher than NIV and variability of this proportion between lines was observed. Significant correlation was found between head infection symptoms and FDK. Head infection was correlated with F. culmorum biomass and NIV concentration in grain. No correlation was found between the FHB index and DON concentration. Similarly, FDK was not correlated with DON content, but it was with NIV content; however, the coefficients were higher than for the FHB index. Fusarium biomass amount was positively correlated with both toxins as well as with the FHB index and FDK. Environmental conditions significantly influenced the DON/NIV ratio in grain. In locations where less F. culmorum biomass was detected, the DON amount was higher than NIV, while in locations where more F. culmorum biomass was observed, NIV prevailed over DON. Full article

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11 pages, 436 KiB

Open AccessArticle

by Katarzyna Bilska, Kinga Stuper-Szablewska, Tomasz Kulik, Maciej Buśko, Dariusz Załuski and Juliusz Perkowski

Toxins 2018, 10(12), 492; https://doi.org/10.3390/toxins10120492 - 24 Nov 2018

Cited by 8 | Viewed by 4505

Abstract

Fungicide application remains amongst the most widely used methods of fungal control in agroecosystems. However, the extensive use of fungicides poses hazards to human health and the natural environment and does not always ensure the effective decrease of mycotoxins in food and feed. [...] Read more.

Fungicide application remains amongst the most widely used methods of fungal control in agroecosystems. However, the extensive use of fungicides poses hazards to human health and the natural environment and does not always ensure the effective decrease of mycotoxins in food and feed. Nowadays, the rising threat from mycotoxin contamination of staple foods has stimulated efforts in developing alternative strategies to control plant pathogenic fungi. A substantial effort is focused on the identification of plant-derived compounds inhibiting mycotoxin production by plant pathogenic fungi. l-Pyroglutamic acid has recently been suggested as playing a role in the response of barley to toxigenic Fusaria. Considering the above, we studied the response of various strains of F. graminearum sensu stricto to different levels of l-pyroglutamic acid on solid YES (yeast extract sucrose) media. l-Pyroglutamic acid decreased the accumulation of trichothecenes in all examined strains. Gene expression studies addressing Tri genes (Tri4, Tri5, and Tri10), which induce the biosynthesis of trichothecenes, revealed the production of mycotoxins by l-pyroglutamic acid to be inhibited at the transcriptional level. Besides inhibitory effects on mycotoxin production, l-pyroglutamic acid exhibited variable and concentration-related effects on phenylpropanoid production by fungi. Accumulation of most of the fungal-derived phenolic acids decreased in the presence of 100 and 400 µg/g of l-pyroglutamic acid. However, a higher dose (800 µg/g) of l-pyroglutamic acid increased the accumulation of trans-cinnamic acid in the media. The accumulation of fungal-derived naringenin increased in the presence of l-pyroglutamic acid. Contrasting results were obtained for quercetin, apigenin, luteolin, and kaempferol, the accumulation of which decreased in the samples treated with 100 and 400 µg/g of l-pyroglutamic acid, whereas the highest l-pyroglutamic acid concentration (800 µg/g) seemed to induce their biosynthesis. The results obtained in this study provide new insights for breeders involved in studies on resistance against Fusaria. Full article

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11 pages, 5538 KiB

Open AccessCommunication

Enhancing the Production of the Fungal Pigment Aurofusarin in Fusarium graminearum

by Klaus Ringsborg Westphal, Rasmus Dam Wollenberg, Florian-Alexander Herbst, Jens Laurids Sørensen, Teis Esben Sondergaard and Reinhard Wimmer

Toxins 2018, 10(11), 485; https://doi.org/10.3390/toxins10110485 - 21 Nov 2018

Cited by 29 | Viewed by 5679

Abstract

There is an increasing demand for products from natural sources, which includes a growing market for naturally-produced colorants. Filamentous fungi produce a vast number of chemically diverse pigments and are therefore explored as an easily accessible source. In this study we examine the [...] Read more.

There is an increasing demand for products from natural sources, which includes a growing market for naturally-produced colorants. Filamentous fungi produce a vast number of chemically diverse pigments and are therefore explored as an easily accessible source. In this study we examine the positive regulatory effect of the transcription factor AurR1 on the aurofusarin gene cluster in Fusarium graminearum. Proteomic analyses showed that overexpression of AurR1 resulted in a significant increase of five of the eleven proteins belonging to the aurofusarin biosynthetic pathway. Further, the production of aurofusarin was increased more than threefold in the overexpression mutant compared to the wild type, reaching levels of 270 mg/L. In addition to biosynthesis of aurofusarin, several yet undescribed putative naphthoquinone/anthraquinone analogue compounds were observed in the overexpression mutant. Our results suggest that it is possible to enhance the aurofusarin production through genetic engineering. Full article

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20 pages, 3744 KiB

Open AccessArticle

Dose and Exposure Time-Dependent Renal and Hepatic Effects of Intraperitoneally Administered Fumonisin B₁ in Rats

by András Szabó, Judit Szabó-Fodor, Mariam Kachlek, Miklós Mézes, Krisztián Balogh, Róbert Glávits, Omeralfaroug Ali, Yarsmin Yunus Zeebone and Melinda Kovács

Toxins 2018, 10(11), 465; https://doi.org/10.3390/toxins10110465 - 9 Nov 2018

Cited by 25 | Viewed by 4174

Abstract

Male Wistar rats were treated intraperitoneally (i.p.) with fumonisin B₁ (FB₁; 0, 20, 50 and 100 mg/kg dietary dose equivalent) for 5 and 10 days (n = 24–24 in each setting) to gain dose- and time-dependent effects on antioxidant [...] Read more.

Male Wistar rats were treated intraperitoneally (i.p.) with fumonisin B₁ (FB₁; 0, 20, 50 and 100 mg/kg dietary dose equivalent) for 5 and 10 days (n = 24–24 in each setting) to gain dose- and time-dependent effects on antioxidant status and oxidative stress response, clinical chemical endpoints and liver, kidney and lung histopathology and lymphocyte damage (genotoxicity). FB₁ decreased feed intake, body weight gain and absolute liver weight, irrespective of the toxin dose. Relative kidney weight increased in the 10-day setting. Linear dose response was found for plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol, urea and creatinine, and exposure time-dependence for plasma creatinine level. The latter was coupled with renal histopathological findings, tubular degeneration and necrosis and the detachment of tubular epithelial cells. The pronounced antioxidant response (reduced glutathione accretion, increasing glutathione peroxidase activity) referred to renal cortical response (5–10 days exposure at 50–100 ppm FB₁). Hepatic alterations were moderate, referring to initial phase lipid peroxidation (exposure time dependent difference of conjugated diene and triene concentrations), and slight functional disturbance (↑ total cholesterol). Lymphocyte DNA damage was moderate, supporting a mild genotoxic effect of FB₁. Full article

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26 pages, 2620 KiB

Open AccessArticle

Deoxynivalenol Affects Cell Metabolism and Increases Protein Biosynthesis in Intestinal Porcine Epithelial Cells (IPEC-J2): DON Increases Protein Biosynthesis

by Constanze Nossol, Peter Landgraf, Stefan Kahlert, Michael Oster, Berend Isermann, Daniela C. Dieterich, Klaus Wimmers, Sven Dänicke and Hermann-Josef Rothkötter

Toxins 2018, 10(11), 464; https://doi.org/10.3390/toxins10110464 - 9 Nov 2018

Cited by 12 | Viewed by 4844

Abstract

Deoxynivalenol (DON) is a toxin found in cereals as well as in processed products such as pasta, and causes substantial economic losses for stock breeding as it induces vomiting, reduced feeding, and reduced growth rates in piglets. Oxidative phosphorylation, TCA-cycle, transcription, and translation [...] Read more.

Deoxynivalenol (DON) is a toxin found in cereals as well as in processed products such as pasta, and causes substantial economic losses for stock breeding as it induces vomiting, reduced feeding, and reduced growth rates in piglets. Oxidative phosphorylation, TCA-cycle, transcription, and translation have been hypothesized to be leading pathways that are affected by DON. We used an application of high and low glucose to examine oxidative phosphorylation and anaerobic glycolysis. A change in the metabolic status of IPEC-J2 was observed and confirmed by microarray data. Measurements of oxygen consumption resulted in a significant reduction, if DON attacks from the basolateral. Furthermore, we found a dose-dependent effect with a significant reduction at 2000 ng/mL. In addition, SLC7A11 and PHB, the genes with the highest regulation in our microarray analyses under low glucose supply, were investigated and showed a variable regulation on protein level. Lactate production and glucose consumption was investigated to examine the impact of DON on anaerobic glycolysis and we observed a significant increase in 2000 bl^high and a decrease in 2000 ap^high. Interestingly, both groups as well as 200 bl^high showed a significant higher de novo protein synthesis when compared to the control. These results indicate the direct or indirect impact of DON on metabolic pathways in IPEC-J2. Full article

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14 pages, 1827 KiB

Open AccessArticle

Effects of a Fusarium Toxin-Contaminated Maize Treated with Sodium Sulfite on Male Piglets in the Presence of an LPS-Induced Acute Inflammation

by Anh-Tuan Tran, Jeannette Kluess, Andreas Berk, Marleen Paulick, Jana Frahm, Dian Schatzmayr, Susanne Kersten and Sven Dänicke

Toxins 2018, 10(10), 419; https://doi.org/10.3390/toxins10100419 - 18 Oct 2018

Cited by 5 | Viewed by 3218

Abstract

We investigated the effects of feeding sodium sulfite (SoS) treated uncontaminated and Fusarium contaminated maize in a porcine lipopolysaccharide (LPS) challenge model. Eighty piglets (7.59 ± 0.92 kg body weight [BW]) were equally assigned to one of four experimental diets containing 10% maize, [...] Read more.

We investigated the effects of feeding sodium sulfite (SoS) treated uncontaminated and Fusarium contaminated maize in a porcine lipopolysaccharide (LPS) challenge model. Eighty piglets (7.59 ± 0.92 kg body weight [BW]) were equally assigned to one of four experimental diets containing 10% maize, either uncontaminated and untreated (CON−, 0.09 mg deoxynivalenol [DON]/kg diet) or uncontaminated and SoS-treated (CON+, wet-preserved with 5 g SoS/kg maize; 0.05 mg DON/kg diet), or prepared with 10% of a Fusarium contaminated maize containing mainly deoxynivalenol (DON), either contaminated and untreated (FUS−, 5.36 mg DON/kg diet), or contaminated and SoS-treated (FUS+, wet-preserved with 5 g SoS/kg maize; 0.83 mg DON/kg diet). At day 42 of experiment, ten pigs of each group were injected intraperitoneally with either 7.5 µg LPS/kg BW or placebo (0.9% NaCl). At 120 min after injection, blood samples were collected to analyse TNF-α, hematological profile, clinical biochemistry as well as the redox status. A significant increase in body temperature and cytokine TNF-α concentration was observed in the LPS-injected piglets. Results for hematology, clinical chemistry and redox status indicate no effects of SoS treatment, with exception of neutrophil counts being significantly more pronounced after feeding the SoS treated FUS maize. In conclusion, SoS treatment of maize did not modulate the LPS-induced acute inflammation. Full article

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15 pages, 654 KiB

Open AccessArticle

Malting of Fusarium Head Blight-Infected Rye (Secale cereale): Growth of Fusarium graminearum, Trichothecene Production, and the Impact on Malt Quality

by Zhao Jin, James Gillespie, John Barr, Jochum J. Wiersma, Mark E. Sorrells, Steve Zwinger, Thomas Gross, Jaime Cumming, Gary C. Bergstrom, Robert Brueggeman, Richard D. Horsley and Paul B. Schwarz

Toxins 2018, 10(9), 369; https://doi.org/10.3390/toxins10090369 - 11 Sep 2018

Cited by 15 | Viewed by 3910

Abstract

This project was initiated with the goal of investigating the malt quality of winter rye cultivars and hybrids grown in the United States in 2014 and 2015, but high levels of deoxynivalenol (DON) were subsequently found in many of the malt samples. DON [...] Read more.

This project was initiated with the goal of investigating the malt quality of winter rye cultivars and hybrids grown in the United States in 2014 and 2015, but high levels of deoxynivalenol (DON) were subsequently found in many of the malt samples. DON levels in 75% of the investigated rye samples (n = 117) were actually below 1.0 mg/kg, as quantified by a gas chromatography combined with electron capture detector (GC-ECD). However, 83% of the samples had DON in excess of 1.0 mg/kg following malting, and the average DON level in malted rye was 10.6 mg/kg. In addition, relatively high levels of 3-acetate DON (3-ADON), 15-acetate DON (15-ADON), nivalenol (NIV), and DON-3-glucoside (D3G) were observed in some rye malts. Our results show that rye grain DON is likely a poor predicator of type B trichothecenes in malt in practice, because high levels of malt DON, 15-ADONm and D3G were produced, even when the rye samples with DON levels below 0.50 mg/kg were processed. Fusarium Tri5 DNA content in rye was highly associated with malt DON levels (r = 0.83) in a small subset of samples (n = 55). The impact of Fusarium infection on malt quality was demonstrated by the significant correlations between malt DON levels and wort viscosity, β-glucan content, wort color, wort p-coumaric acid content, and total phenolic content. Additional correlations of rye Fusarium Tri5 DNA contents with malt diastatic power (DP), wort free amino nitrogen (FAN) content, and arabinoxylan content were observed. Full article

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21 pages, 6105 KiB

Open AccessArticle

Biomarker Evaluation and Toxic Effects of an Acute Oral and Systemic Fumonisin Exposure of Pigs with a Special Focus on Dietary Fumonisin Esterase Supplementation

by Hanna Schertz, Sven Dänicke, Jana Frahm, Dian Schatzmayr, Ilse Dohnal, Gerlinde Bichl, Heidi E. Schwartz-Zimmermann, Sonia Colicchia, Gerhard Breves, Jens P. Teifke and Jeannette Kluess

Toxins 2018, 10(7), 296; https://doi.org/10.3390/toxins10070296 - 17 Jul 2018

Cited by 19 | Viewed by 6000

Abstract

The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed. It causes a disruption of sphingolipid metabolism and pulmonary, hepatic, and immunological lesions in pigs depending on the exposure scenario. One sensitive biomarker for FB1 exposure is the sphinganine (Sa) to sphingosine [...] Read more.

The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed. It causes a disruption of sphingolipid metabolism and pulmonary, hepatic, and immunological lesions in pigs depending on the exposure scenario. One sensitive biomarker for FB1 exposure is the sphinganine (Sa) to sphingosine (So) ratio in blood. The fumonisin esterase FumD, which can be used as a feed additive, converts FB1 into the much less toxic metabolite hydrolyzed FB1 (HFB1). We conducted a single-dose study with barrows allocated to one of five treatments: (1) control (feed, 0.9% NaCl intravenously iv), (2) 139 nmol FB1 or (3) HFB1/kg BW iv, (4) 3425 nmol FB1/kg BW orally (po), or (5) 3321 nmol FB1/kg BW and 240 U FumD/kg feed po. The Sa/So ratio of iv and po FB1 administered groups was significantly elevated in blood and Liquor cerebrospinalis, but no fumonisin-associated differences were reflected in other endpoints. Neither clinical lung affections nor histopathological pulmonary lesions were detected in either group, while some parameters of hematology and clinical biochemistry showed a treatment–time interaction. FumD application resulted in Sa/So ratios comparable to the control, indicating that the enzymatic treatment was effectively preventing the fumonisin-induced disruption of sphingolipid metabolism. Full article

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2 pages, 1194 KiB

Open AccessArticle

Chronic Effects of Fusarium Mycotoxins in Rations with or without Increased Concentrate Proportion on the Insulin Sensitivity in Lactating Dairy Cows

by Asako Kinoshita, Christina Keese, Ulrich Meyer, Alexander Starke, Christine Wrenzycki, Sven Dänicke and Jürgen Rehage

Toxins 2018, 10(5), 188; https://doi.org/10.3390/toxins10050188 - 8 May 2018

Cited by 10 | Viewed by 5131

Abstract

The objective of this study was to investigate the effect of long-term exposure to a Fusarium toxin deoxynivalenol (DON, 5 mg/kg DM) on the energy metabolism in lactating cows fed diets with different amounts of concentrate. In Period 1 27 German Holstein cows [...] Read more.

The objective of this study was to investigate the effect of long-term exposure to a Fusarium toxin deoxynivalenol (DON, 5 mg/kg DM) on the energy metabolism in lactating cows fed diets with different amounts of concentrate. In Period 1 27 German Holstein cows were assigned to two groups and fed a control or mycotoxin-contaminated diet with 50% concentrate for 11 weeks. In Period 2 each group was further divided and fed either a diet containing 30% or 60% concentrate for 16 weeks. Blood samples were collected in week 0, 4, 8, 15, 21, and 27 for calculation of the Revised Quantitative Insulin Sensitivity Check Index and biopsy samples of skeletal muscle and the liver in w 0, 15, and 27 for analysis by real-time RT-qPCR. The DON-fed groups presented lower insulin sensitivities than controls at week 27. Concomitantly, muscular mRNA expression of insulin receptors and hepatic mRNA expression of glucose transporter 2 and key enzymes for gluconeogenesis and fatty acid metabolism were lower in DON-fed cows compared to the control. The study revealed no consistent evidence that DON effects were modified by dietary concentrate levels. In conclusion, long-term dietary DON intake appears to have mild effects on energy metabolism in lactating dairy cows. Full article

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13 pages, 994 KiB

Open AccessArticle

Development of an Analytical Method for Simultaneous Determination of the Modified Forms of 4,15-Diacetoxyscirpenol and their Occurrence in Japanese Retail Food

by Tomoya Yoshinari, Nanami Takeda, Maiko Watanabe and Yoshiko Sugita-Konishi

Toxins 2018, 10(5), 178; https://doi.org/10.3390/toxins10050178 - 26 Apr 2018

Cited by 15 | Viewed by 4665

Abstract

4,15-Diacetoxyscirpenol (4,15-DAS) is a type A trichothecene mycotoxin produced by Fusarium species. Four modified forms of 4,15-DAS including 7-hydroxydiacetoxyscirpenol, 7,8-dihydroxydiacetoxyscirpenol, 4β,8α,15-triacetoxy-3α,7α-dihydroxy-12,13-epoxytrichothec-9-ene and 4,15-diacetylnivalenol were purified from cultures of F. equiseti. An analytical method using a multifunctional column has been developed for the [...] Read more.

4,15-Diacetoxyscirpenol (4,15-DAS) is a type A trichothecene mycotoxin produced by Fusarium species. Four modified forms of 4,15-DAS including 7-hydroxydiacetoxyscirpenol, 7,8-dihydroxydiacetoxyscirpenol, 4β,8α,15-triacetoxy-3α,7α-dihydroxy-12,13-epoxytrichothec-9-ene and 4,15-diacetylnivalenol were purified from cultures of F. equiseti. An analytical method using a multifunctional column has been developed for the simultaneous determination of 4,15-DAS, its four modified forms, T-2 toxin, HT-2 toxin and neosolaniol in cereals. The performance of the current method was evaluated, and a total of 248 samples of five different commodities were analyzed for over two years by this method. 4,15-DAS was detected in Job’s tears products, corn flour and azuki bean, but it was not found in wheat flour or rye flour. The four modified forms of 4,15-DAS were detected in samples of Job’s tears products, contaminated by 4,15-DAS. This is the first report on quantification of the modified forms of 4,15-DAS in cereals. Full article

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14 pages, 9681 KiB

Open AccessArticle

Bovine Peripheral Blood Mononuclear Cells Are More Sensitive to Deoxynivalenol Than Those Derived from Poultry and Swine

by Barbara Novak, Eleni Vatzia, Alexandra Springler, Alix Pierron, Wilhelm Gerner, Nicole Reisinger, Sabine Hessenberger, Gerd Schatzmayr and Elisabeth Mayer

Toxins 2018, 10(4), 152; https://doi.org/10.3390/toxins10040152 - 11 Apr 2018

Cited by 19 | Viewed by 6340

Abstract

Deoxynivalenol (DON) is one of the most prevalent mycotoxins, contaminating cereals and cereal-derived products. Its derivative deepoxy-deoxynivalenol (DOM-1) is produced by certain bacteria, which either occur naturally or are supplemented in feed additive. DON-induced impairments in protein synthesis are particularly problematic for highly [...] Read more.

Deoxynivalenol (DON) is one of the most prevalent mycotoxins, contaminating cereals and cereal-derived products. Its derivative deepoxy-deoxynivalenol (DOM-1) is produced by certain bacteria, which either occur naturally or are supplemented in feed additive. DON-induced impairments in protein synthesis are particularly problematic for highly proliferating immune cells. This study provides the first comparison of the effects of DON and DOM-1 on the concanavalin A-induced proliferation of porcine, chicken, and bovine peripheral blood mononuclear cells (PBMCs). Therefore, isolated PBMCs were treated with DON (0.01–3.37 µM) and DOM-1 (1.39–357 µM) separately, and proliferation was measured using a bromodeoxyuridine (BrdU) assay. Although pigs are considered highly sensitive to DON, the present study revealed a substantially higher sensitivity of bovine (IC50 = 0.314 µM) PBMCs compared to chicken (IC50 = 0.691 µM) and porcine (IC50 = 0.693 µM) PBMCs. Analyses on the proliferation of bovine T-cell subsets showed that all major subsets, namely, CD4⁺, CD8β⁺, and γδ T cells, were affected to a similar extent. In contrast, DOM-1 did not affect bovine PBMCs, but reduced the proliferation of chicken and porcine PBMCs at the highest tested concentration (357 µM). Results confirm the necessity of feed additives containing DON-to-DOM-1-transforming bacteria and highlights species-specific differences in the DON sensitivity of immune cells. Full article

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23 pages, 1226 KiB

Open AccessArticle

Oral and Intravenous Fumonisin Exposure in Pigs—A Single-Dose Treatment Experiment Evaluating Toxicokinetics and Detoxification

by Hanna Schertz, Jeannette Kluess, Jana Frahm, Dian Schatzmayr, Ilse Dohnal, Gerlinde Bichl, Heidi Schwartz-Zimmermann, Gerhard Breves and Sven Dänicke

Toxins 2018, 10(4), 150; https://doi.org/10.3390/toxins10040150 - 5 Apr 2018

Cited by 15 | Viewed by 5381

Abstract

We examined the toxicokinetics of fumonisin B₁ (FB1) and its main metabolites after single dose application intravenously (iv) of 139 nmol FB1 or hydrolyzed FB1 (HFB1)/kg bodyweight (BW) in barrows (BW: 34.4 kg ± 2.7 kg), as well as the [...] Read more.

We examined the toxicokinetics of fumonisin B₁ (FB1) and its main metabolites after single dose application intravenously (iv) of 139 nmol FB1 or hydrolyzed FB1 (HFB1)/kg bodyweight (BW) in barrows (BW: 34.4 kg ± 2.7 kg), as well as the toxicokinetics of FB1, FB2, FB3 and FB1 bioavailability from oral exposure (3425 nmol FB1/kg BW, on top of ration). Additionally, detoxification efficacy of FumD (240 U/kg feed; 3321 nmol FB1/kg BW), a fumonisin esterase, was examined for oral fumonisin application. Urine and feces were collected quantitatively and serum samples were taken over a period of 120 h. Serum toxicokinetics of FB1iv showed a short distribution half-life of 6 min followed by a longer elimination half-life of 36 min. After HFB1iv administration, serum clearance was three times higher compared to FB1iv group (5.6 and 1.8 L/kg/h respectively) which together with a 5-times higher volume of distribution indicates that HFB1 is more rapidly cleared from systemic circulation but distributed more extensively into the extravasal space than FB1. The bioavailability of FB1 in orally exposed pigs was 5.2% (incl. metabolites). Moreover, we found a significant reduction of FB1 bioavailability by 90% caused by the action of fumonisin esterase in the gastrointestinal tract, clearly demonstrating the efficacy of FumD. Full article

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15 pages, 682 KiB

Open AccessArticle

Effects of High Levels of Deoxynivalenol and Zearalenone on Growth Performance, and Hematological and Immunological Parameters in Pigs

by Kondreddy Eswar Reddy, Jaeyong Song, Hyun-Jeong Lee, Minseok Kim, Dong-Wook Kim, Hyun Jung Jung, Bumseok Kim, Yookyung Lee, Dongjo Yu, Dong-Woon Kim, Young Kyoon Oh and Sung Dae Lee

Toxins 2018, 10(3), 114; https://doi.org/10.3390/toxins10030114 - 7 Mar 2018

Cited by 63 | Viewed by 7250

Abstract

Background: Deoxynivalenol (DON) and zearalenone (ZEN) are common food contaminants produced by Fusarium sp. Mycotoxins are a potential health hazard because of their toxicological effects on both humans and farmed animals. Methods: We analyzed three groups of pigs: a control group (fed [...] Read more.

Background: Deoxynivalenol (DON) and zearalenone (ZEN) are common food contaminants produced by Fusarium sp. Mycotoxins are a potential health hazard because of their toxicological effects on both humans and farmed animals. Methods: We analyzed three groups of pigs: a control group (fed a standard diet), and the DON and ZEN groups, fed a diet containing 8 mg/kg DON and 0.8 mg/kg ZEN respectively, for four weeks. Results: DON and ZEN exposure decreased body weight (BW), average daily feed intake (ADFI), food conversion rate (FCR), and the serum levels of immunoglobulin (Ig)G and IgM. The total antioxidant levels significantly decreased in serum and increased in urine samples of both treatment groups. Additionally, DON and ZEN exposure increased serotonin levels in urine. Hematological parameters were not affected by the investigated toxins. Microscopic lesions were evident in sections of kidneys from either treatment group: we found sporadic interstitial nephritis in the DON group and renal glomerulus atrophy in the ZEN group. The expression levels of inflammatory cytokines and chemokine marker genes were reduced in tissues from DON- and ZEN-exposed pigs. Conclusions: chronic ingestion of high doses of DON and ZEN alters the immune response and causes organs damage, and might be associated with various diseases in pigs. Full article

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13 pages, 561 KiB

Open AccessArticle

Assessment of Urinary Deoxynivalenol Biomarkers in UK Children and Adolescents

by Maria Papageorgiou, Liz Wells, Courtney Williams, Kay White, Barbara De Santis, Yunru Liu, Francesca Debegnach, Brunella Miano, Giorgio Moretti, Stephanie Greetham, Carlo Brera, Stephen L Atkin, Laura J Hardie and Thozhukat Sathyapalan

Toxins 2018, 10(2), 50; https://doi.org/10.3390/toxins10020050 - 23 Jan 2018

Cited by 41 | Viewed by 5645

Abstract

Deoxynivalenol (DON), the mycotoxin produced mainly by Fusarium graminearum and found in contaminated cereal-based foodstuff, has been consistently detected in body fluids in adults. Available data in children and adolescents are scarce. This study assessed urinary DON concentrations in children aged 3–9 years [...] Read more.

Deoxynivalenol (DON), the mycotoxin produced mainly by Fusarium graminearum and found in contaminated cereal-based foodstuff, has been consistently detected in body fluids in adults. Available data in children and adolescents are scarce. This study assessed urinary DON concentrations in children aged 3–9 years (n = 40) and adolescents aged 10–17 years (n = 39) in the UK. Morning urine samples were collected over two consecutive days and analysed for free DON (un-metabolised form), DON-glucuronides (DON-GlcA), deepoxy deoxynivalenol (DOM-1), and total DON (sum of free DON, DON-GlcA, and DOM-1). Total DON was detected in the urine of >95% of children and adolescents on both days. Mean total DON concentrations (ng/mg creatinine) were 41.6 and 21.0 for children and adolescents, respectively. The greatest total DON levels were obtained in female children on both days (214 and 219 ng/mg creatinine on days 1 and 2, respectively). Free DON and DON-GlcA were detected in most urine specimens, whereas DOM-1 was not present in any sample. Estimation of dietary DON exposure suggested that 33–63% of children and 5–46% of adolescents exceeded current guidance regarding the maximum provisional tolerable daily intake (PMTDI) for DON. Although moderate mean urinary DON concentrations were shown, the high detection frequency of urinary DON, the maximum biomarker concentrations, and estimated dietary DON exposure are concerning. Full article

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16 pages, 6550 KiB

Open AccessArticle

ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

by Wang-Long Zheng, Bing-Jie Wang, Ling Wang, Yu-Ping Shan, Hui Zou, Rui-Long Song, Tao Wang, Jian-Hong Gu, Yan Yuan, Xue-Zhong Liu, Guo-Qiang Zhu, Jian-Fa Bai, Zong-Ping Liu and Jian-Chun Bian

Toxins 2018, 10(1), 24; https://doi.org/10.3390/toxins10010024 - 1 Jan 2018

Cited by 95 | Viewed by 7504

Abstract

Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied [...] Read more.

Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress and the ATP/AMPK pathway in ZEA-induced cell-cycle arrest and cell apoptosis was explored by using the antioxidant NAC, ER stress inhibitor 4-PBA and the AMPK inhibitor dorsomorphin, respectively. The results revealed that ZEA inhibited the cell proliferation, influenced the distribution of the cell cycle and induced cell apoptosis through the ATP/AMPK pathway. The ATP/AMPK pathway was regulated by ER stress that was induced by ROS generation after exposure to ZEA. Taking these together, this study provided evidence that ROS regulated the process of ZEA-induced cell cycle arrest and cell apoptosis through ER stress and the ATP/AMPK signal ways. Full article

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2055 KiB

Open AccessArticle

Primary and Immortalized Human Respiratory Cells Display Different Patterns of Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and Fusarenon-X

by Silvia Ferreira Lopes, Gaëlle Vacher, Eleonora Ciarlo, Dessislava Savova-Bianchi, Thierry Roger and Hélène Niculita-Hirzel

Toxins 2017, 9(11), 337; https://doi.org/10.3390/toxins9110337 - 25 Oct 2017

Cited by 18 | Viewed by 5923

Abstract

The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are structurally related secondary metabolites frequently produced by Fusarium on wheat. Consequently, DON, NIV and FX contaminate wheat dusts, exposing grain workers to toxins by inhalation. Those trichothecenes at low, relevant, [...] Read more.

The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are structurally related secondary metabolites frequently produced by Fusarium on wheat. Consequently, DON, NIV and FX contaminate wheat dusts, exposing grain workers to toxins by inhalation. Those trichothecenes at low, relevant, exposition concentrations have differential effects on intestinal cells, but whether such differences exist with respiratory cells is mostly unknown, while it is required to assess the combined risk of exposure to mycotoxins. The goal of the present study was to compare the effects of DON, NIV and FX alone or in combination on the viability and IL-6 and IL-8-inducing capacity of human epithelial cells representative of the respiratory tract: primary human airway epithelial cells of nasal (hAECN) and bronchial (hAECB) origin, and immortalized human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines. We report that A549 cells are particularly resistant to the cytotoxic effects of mycotoxins. FX is more toxic than DON and NIV for all epithelial cell types. Nasal and bronchial primary cells are more sensitive than bronchial and alveolar cell lines to combined mycotoxin mixtures at low concentrations, although they are less sensitive to mycotoxins alone. Interactions between mycotoxins at low concentrations are rarely additive and are observed only for DON/NIV and NIV/FX on hAECB cells and DON/NIV/FX on A549 cells. Most interactions at low mycotoxin concentrations are synergistic, antagonistic interactions being observed only for DON/FX on hAECB, DON/NIV on 16HBE14o- and NIV/FX on A549 cells. DON, NIV and FX induce, albeit at different levels, IL-6 and IL-8 release by all cell types. However, NIV and FX at concentrations of low cytotoxicity induce IL-6 release by hAECB and A549 cells, and IL-8 release by hAECN cells. Overall, these data suggest that combined exposure to mycotoxins at low concentrations have a stronger effect on primary nasal epithelial cells than on bronchial epithelial cells and activate different inflammatory pathways. This information is particularly relevant for future studies about the hazard of occupational exposure to mycotoxins by inhalation and its impact on the respiratory tract. Full article

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4379 KiB

Open AccessArticle

Chronic Exposure to the Fusarium Mycotoxin Deoxynivalenol: Impact on Performance, Immune Organ, and Intestinal Integrity of Slow-Growing Chickens

by Stephanie S. Chen, Yi-Hung Li and Mei-Fong Lin

Toxins 2017, 9(10), 334; https://doi.org/10.3390/toxins9100334 - 20 Oct 2017

Cited by 53 | Viewed by 6945

Abstract

This study investigates the long-term effects of deoxynivalenol (DON) consumption on avian growth performance, on the proliferation, apoptosis, and DNA damage of spleen cells, and on intestinal integrity. Two hundred and eight 5-day-old black-feathered Taiwan country chickens were fed diets containing 0, 2, [...] Read more.

This study investigates the long-term effects of deoxynivalenol (DON) consumption on avian growth performance, on the proliferation, apoptosis, and DNA damage of spleen cells, and on intestinal integrity. Two hundred and eight 5-day-old black-feathered Taiwan country chickens were fed diets containing 0, 2, 5, and 10 mg/kg of DON for 16 weeks. Body weight gain of male birds in the 2 mg/kg group was significantly lower than that in the 5 mg/kg group. At the end of trial, feeding DON-contaminated diets of 5 mg/kg resulted in heavier spleens. Moreover, the increase in DON induced cellular proliferation, apoptosis, and DNA damage signals in the spleen, the exception being female birds fed 10 mg/kg of DON showing reduced proliferation. Expression of claudin-5 was increased in jejunum of female birds fed 2 and 5 mg/kg of DON, whereas decreased expression levels were found in male birds. In conclusion, our results verified that DON may cause a disturbance to the immune system and alter the intestinal barrier in Taiwan country chickens, and may also lead to discrepancies in growth performances in a dose- and sex-dependent manner. Full article

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Open AccessArticle

Gas Chromatography-Mass Spectrometry for Metabolite Profiling of Japanese Black Cattle Naturally Contaminated with Zearalenone and Sterigmatocystin

by Katsuki Toda, Emiko Kokushi, Seiichi Uno, Ayaka Shiiba, Hiroshi Hasunuma, Yasuo Fushimi, Missaka P. B. Wijayagunawardane, Chunhua Zhang, Osamu Yamato, Masayasu Taniguchi, Johanna Fink-Gremmels and Mitsuhiro Takagi

Toxins 2017, 9(10), 294; https://doi.org/10.3390/toxins9100294 - 21 Sep 2017

Cited by 18 | Viewed by 5772

Abstract

The objective of this study was to evaluate the metabolic profile of cattle fed with or without zearalenone (ZEN) and sterigmatocystin (STC)-contaminated diets using a gas chromatography-mass spectrometry metabolomics approach. Urinary samples were collected from individual animals (n = 6 per herd) [...] Read more.

The objective of this study was to evaluate the metabolic profile of cattle fed with or without zearalenone (ZEN) and sterigmatocystin (STC)-contaminated diets using a gas chromatography-mass spectrometry metabolomics approach. Urinary samples were collected from individual animals (n = 6 per herd) from fattening female Japanese Black (JB) cattle herds (23 months old, 550–600 kg). Herd 1 had persistently high urinary ZEN and STC concentrations due to the presence of contaminated rice straw. Herd 2, the second female JB fattening herd (23 months old, 550–600 kg), received the same dietary feed as Herd 1, with non-contaminated rice straw. Urine samples were collected from Herd 1, two weeks after the contaminated rice straw was replaced with uncontaminated rice straw (Herd 1N). Identified metabolites were subjected to principal component analysis (PCA) and ANOVA. The PCA revealed that the effects on cattle metabolites depended on ZEN and STC concentrations. The contamination of cattle feed with multiple mycotoxins may alter systemic metabolic processes, including metabolites associated with ATP generation, amino acids, glycine-conjugates, organic acids, and purine bases. The results obtained from Herd 1N indicate that a two-week remedy period was not sufficient to improve the levels of urinary metabolites, suggesting that chronic contamination with mycotoxins may have long-term harmful effects on the systemic metabolism of cattle. Full article

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Open AccessArticle

Sinapic Acid Affects Phenolic and Trichothecene Profiles of F. culmorum and F. graminearum Sensu Stricto

by Tomasz Kulik, Kinga Stuper-Szablewska, Katarzyna Bilska, Maciej Buśko, Anna Ostrowska-Kołodziejczak, Dariusz Załuski and Juliusz Perkowski

Toxins 2017, 9(9), 264; https://doi.org/10.3390/toxins9090264 - 28 Aug 2017

Cited by 19 | Viewed by 6688

Abstract

Plant-derived compounds for reducing the mycotoxin load in food and feed have become a rapidly developing research field of importance for plant breeding efforts and in the search for natural fungicides. In this study, toxigenic strains of Fusarium culmorum and F. graminearum sensu [...] Read more.

Plant-derived compounds for reducing the mycotoxin load in food and feed have become a rapidly developing research field of importance for plant breeding efforts and in the search for natural fungicides. In this study, toxigenic strains of Fusarium culmorum and F. graminearum sensu stricto were exposed to sinapic acid on solid YES media at levels close to those reported in wheat bran. Fusaria produced phenolic acids, whose accumulation was decreased by exogenous sinapic acid. Strains exposed to the lowest doses of sinapic acid showed more efficient reduction of phenolic acid production than fungi kept at higher concentrations of this compound. Fungi reduced exogenous sinapic acid, leading to the formation of syringic aldehyde. Treatment with sinapic acid led to a dramatic accumulation of its parent compound ferulic acid, presumably due to inhibition of the further conversion of this phenolic compound. Exogenous sinapic acid decreased the production of trichothecenes by fungi. Higher doses of sinapic acid resulted in more efficient reduction of mycotoxin accumulation in the media. Gene expression studies of Tri genes responsible for trichothecene biosynthesis (Tri4, Tri5 and Tri10) proved that the inhibition of mycotoxin production by sinapic acid occurred at the transcriptional level. Fusaria respond to sinapic acid by stimulation of ergosterol biosynthesis. Full article

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Open AccessFeature PaperArticle

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

by James J. Pestka, Erica S. Clark, Heidi E. Schwartz-Zimmermann and Franz Berthiller

Toxins 2017, 9(8), 240; https://doi.org/10.3390/toxins9080240 - 4 Aug 2017

Cited by 23 | Viewed by 6612 | Correction

Abstract

Based on prior observations that deoxynivalenol (DON) toxicity is sex-dependent, we compared metabolism and clearance of this toxin in male and female mice. Following intraperitoneal challenge with 1 mg/kg bw DON, the dose used in the aforementioned toxicity study, ELISA and LC–MS/MS analyses [...] Read more.

Based on prior observations that deoxynivalenol (DON) toxicity is sex-dependent, we compared metabolism and clearance of this toxin in male and female mice. Following intraperitoneal challenge with 1 mg/kg bw DON, the dose used in the aforementioned toxicity study, ELISA and LC–MS/MS analyses revealed that by 24 h, most DON and DON metabolites were excreted via urine (49–86%) as compared to feces (1.2–8.3%). Females excreted DON and its principal metabolites (DON-3-, DON-8,15 hemiketal-8-, and iso-DON-8-glucuronides) in urine more rapidly than males. Metabolite concentrations were typically 2 to 4 times higher in the livers and kidneys of males than females from 1 to 4 h after dosing. Trace levels of DON-3-sulfate and DON-15-sulfate were found in urine, liver and kidneys from females but not males. Fecal excretion of DON and DON sulfonates was approximately 2-fold greater in males than females. Finally, decreased DON clearance rates in males could not be explained by glucuronidation activities in liver and kidney microsomes. To summarize, increased sensitivity of male mice to DON’s toxic effects as compared to females corresponds to decreased ability to clear the toxin via urine but did not appear to result from differences in toxin metabolism. Full article

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Open AccessArticle

The Occurrence of Zearalenone in South Korean Feedstuffs between 2009 and 2016

by Hansub Chang, Woori Kim, Ju-Hee Park, Dongho Kim, Choong-Ryeol Kim, Soohyun Chung and Chan Lee

Toxins 2017, 9(7), 223; https://doi.org/10.3390/toxins9070223 - 15 Jul 2017

Cited by 50 | Viewed by 5665

Abstract

Mycotoxins produced by Fusarium plant pathogen species have harmful effects on humans and livestock by natural contamination in food and feed. Zearalenone, one of the well-known Fusarium mycotoxins, causes hyperestrogenism and toxicosis resulting in reproductive dysfunction in animals. This study investigated the occurrence [...] Read more.

Mycotoxins produced by Fusarium plant pathogen species have harmful effects on humans and livestock by natural contamination in food and feed. Zearalenone, one of the well-known Fusarium mycotoxins, causes hyperestrogenism and toxicosis resulting in reproductive dysfunction in animals. This study investigated the occurrence of zearalenone in feedstuffs (compound feeds, feed ingredients) between 2009 and 2016 in South Korea to obtain information on zearalenone contamination in feeds for management. A total of 653 animal feed samples (494 compound feeds, 159 feed ingredients) produced domestically were sampled five times from 2009 to 2016 (2009, 2010, 2012, 2014, and 2016) from feed factories in South Korea. The levels of zearalenone were analyzed every year by high-performance liquid chromatography (HPLC) after pretreatment with an immunoaffinity column showing limit of detection (LOD) and limit of quantification (LOQ) of 0.1–3 μg/kg and 0.3–8 μg/kg, respectively. Four feed samples out of 494 compound feeds exceeded the EU and South Korea commission regulations over the eight-year test period, and no feed ingredients exceeded the guidelines. Full article

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Open AccessArticle

trans-Cinnamic and Chlorogenic Acids Affect the Secondary Metabolic Profiles and Ergosterol Biosynthesis by Fusarium culmorum and F. graminearum Sensu Stricto

by Tomasz Kulik, Kinga Stuper-Szablewska, Katarzyna Bilska, Maciej Buśko, Anna Ostrowska-Kołodziejczak, Dariusz Załuski and Juliusz Perkowski

Toxins 2017, 9(7), 198; https://doi.org/10.3390/toxins9070198 - 22 Jun 2017

Cited by 24 | Viewed by 5673

Abstract

Plant-derived compounds limiting mycotoxin contamination are currently of major interest in food and feed production. However, their potential application requires an evaluation of their effects on fungal secondary metabolism and membrane effects. In this study, different strains of Fusarium culmorum and F. graminearum [...] Read more.

Plant-derived compounds limiting mycotoxin contamination are currently of major interest in food and feed production. However, their potential application requires an evaluation of their effects on fungal secondary metabolism and membrane effects. In this study, different strains of Fusarium culmorum and F. graminearum sensu stricto were exposed to trans-cinnamic and chlorogenic acids on solid YES media. Fusaria produced phenolic acids, whose accumulation was lowered by exogenous phenolic compounds. In addition, fungi reduced exogenous phenolic acids, leading either to their conversion or degradation. trans-Cinnamic acid was converted to caffeic and ferulic acids, while chlorogenic acid was degraded to caffeic acid. The latter underwent further degradation to protocatechuic acid. Fungal-derived trans-cinnamic acid, as the first intermediate of the shikimate pathway, increased after chlorogenic acid treatment, presumably due to the further inhibition of the conversion of trans-cinnamic acid. Exogenous trans-cinnamic and chlorogenic acid displayed the inhibition of mycotoxin production by Fusaria, which appeared to be largely dependent on the phenolic compound and its concentration and the assayed strain. Exogenous phenolic acids showed different effects on ergosterol biosynthesis by fungi. It was found that the production of this membrane sterol was stimulated by trans-cinnamic acid, while chlorogenic acid negatively impacted ergosterol biosynthesis, suggesting that phenolic acids with stronger antifungal activities may upregulate ergosterol biosynthesis by Fusaria. This paper reports on the production of phenolic acids by Fusaria for the first time. Full article

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Open AccessArticle

Metabolism of Zearalenone and Its Major Modified Forms in Pigs

by Sabina B. Binder, Heidi E. Schwartz-Zimmermann, Elisabeth Varga, Gerlinde Bichl, Herbert Michlmayr, Gerhard Adam and Franz Berthiller

Toxins 2017, 9(2), 56; https://doi.org/10.3390/toxins9020056 - 8 Feb 2017

Cited by 124 | Viewed by 10298

Abstract

The Fusarium mycotoxin zearalenone (ZEN) can be conjugated with polar molecules, like sugars or sulfates, by plants and fungi. To date, the fate of these modified forms of ZEN has not yet been elucidated in animals. In order to investigate whether ZEN conjugates [...] Read more.

The Fusarium mycotoxin zearalenone (ZEN) can be conjugated with polar molecules, like sugars or sulfates, by plants and fungi. To date, the fate of these modified forms of ZEN has not yet been elucidated in animals. In order to investigate whether ZEN conjugates contribute to the total ZEN exposure of an individual, ZEN (10 µg/kg b.w.) and equimolar amounts of two of its plant metabolites (ZEN-14-O-β-glucoside, ZEN-16-O-β-glucoside) and of one fungal metabolite (ZEN-14-sulfate) were orally administered to four pigs as a single bolus using a repeated measures design. The concentrations of ZEN, its modified forms and its mammalian metabolites ZEN-14-glucuronide, α-zearalenol (α-ZEL) and α-ZEL-14-glucuronide in excreta were analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) based methods. The biological recovery of ZEN in urine was 26% ± 10%, the total biological recovery in excreta was 40% ± 8%. Intact ZEN-14-sulfate, ZEN-14-O-β-glucoside and ZEN-16-O-β-glucoside were neither detected in urine nor in feces. After ZEN-14-sulfate application, 19% ± 5% of the administered dose was recovered in urine. In feces, no ZEN metabolites were detected. The total biological recoveries of ZEN-14-O-β-glucoside and ZEN-16-O-β-glucoside in the form of their metabolites in urine were 19% ± 11% and 13% ± 7%, respectively. The total biological recoveries in urine and feces amounted to 48% ± 7% and 34 ± 3%. An explanation for the low biological recoveries could be extensive metabolization by intestinal bacteria to yet unknown metabolites. In summary, ZEN-14-sulfate, ZEN-14-O-β-glucoside, and ZEN-16-O-β-glucoside were completely hydrolyzed in the gastrointestinal tract of swine, thus contributing to the overall toxicity of ZEN. Full article

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2016

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Open AccessCommunication

Fast Screening of Antibacterial Compounds from Fusaria

by Teis Esben Sondergaard, Marlene Fredborg, Ann-Maria Oppenhagen Christensen, Sofie K. Damsgaard, Nikoline F. Kramer, Henriette Giese and Jens Laurids Sørensen

Toxins 2016, 8(12), 355; https://doi.org/10.3390/toxins8120355 - 29 Nov 2016

Cited by 32 | Viewed by 6601

Abstract

Bio-guided screening is an important method to identify bioactive compounds from fungi. In this study we applied a fast digital time-lapse microscopic method for assessment of the antibacterial properties of secondary metabolites from the fungal genus Fusarium. Here antibacterial effects could be [...] Read more.

Bio-guided screening is an important method to identify bioactive compounds from fungi. In this study we applied a fast digital time-lapse microscopic method for assessment of the antibacterial properties of secondary metabolites from the fungal genus Fusarium. Here antibacterial effects could be detected for antibiotic Y, aurofusarin, beauvericin, enniatins and fusaric acid after six hours of cultivation. The system was then used in a bio-guided screen of extracts from 14 different Fusarium species, which had been fractionated by HPLC. In this screen, fractions containing the red pigments aurofusarin and bikaverin showed effects against strains of Lactobacillus and Bifidobacterium. The IC₅₀ for aurofusarin against Lactobacillus acidophilus was 8 µM, and against Bifidobacterium breve it was 64 µM. Aurofusarin only showed an effect on probiotic bacteria, leading to the speculation that only health-promoting bacteria with a positive effect in the gut system are affected. Full article

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Open AccessArticle

Deoxynivalenol and Its Modified Forms: Are There Major Differences?

by Arash Alizadeh, Saskia Braber, Peyman Akbari, Aletta Kraneveld, Johan Garssen and Johanna Fink-Gremmels

Toxins 2016, 8(11), 334; https://doi.org/10.3390/toxins8110334 - 16 Nov 2016

Cited by 48 | Viewed by 7041

Abstract

Considering the diverse toxic effects of the Fusarium toxin deoxynivalenol (DON), its common occurrence in wheat-based products, and its stability during processing, DON constitutes an increasing health concern for humans and animals. In addition to the parent compound DON, human and animal exposure [...] Read more.

Considering the diverse toxic effects of the Fusarium toxin deoxynivalenol (DON), its common occurrence in wheat-based products, and its stability during processing, DON constitutes an increasing health concern for humans and animals. In addition to the parent compound DON, human and animal exposure encompasses the acetylated fungal metabolites 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl-deoxynivalenol (15ADON) as well as the plant-derived DON-glucoside (DON3G) and the bacterial product de-epoxy-DON (DOM-1). In the current study we used the well-established Caco-2 cell model to compare the effects of these naturally occurring forms of DON on cell viability and markers of barrier integrity, as well as on the release of the pro-inflammatory chemokine chemokine CXC motif ligand (CXCL8). Results show that 3ADON is less potent in inducing adverse effects on barrier integrity when compared to DON, whereas 15ADON appears to be slightly more potent than DON. In contrast, DON3G and DOM-1 exerted no measurable adverse effects on the intestinal barrier. It was also demonstrated that galacto-oligosaccharides (GOS) are able to protect epithelial cells against DON and its acetylated forms, which suggests that GOS are beneficial food additives in the protection of vulnerable segments of the human population against adverse effects of DON and its derivatives. Full article

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Open AccessArticle

Determination of Deoxynivalenol in the Urine of Pregnant Women in the UK

by Liz Wells, Laura Hardie, Courtney Williams, Kay White, Yunru Liu, Barbara De Santis, Francesca Debegnach, Georgio Moretti, Stephanie Greetham, Carlo Brera, Alan Rigby, Stephen Atkin and Thozhukat Sathyapalan

Toxins 2016, 8(11), 306; https://doi.org/10.3390/toxins8110306 - 25 Oct 2016

Cited by 21 | Viewed by 5880

Abstract

Deoxynivalenol (DON) is one of the most commonly occurring trichothecenes, produced mainly by Fusarium graminearum. Little is known about the effect of DON exposure or the levels of DON exposure that occur during pregnancy. The project aimed to provide data on levels [...] Read more.

Deoxynivalenol (DON) is one of the most commonly occurring trichothecenes, produced mainly by Fusarium graminearum. Little is known about the effect of DON exposure or the levels of DON exposure that occur during pregnancy. The project aimed to provide data on levels of total DON and de-epoxi Deoxynivalenol (DOM-1) in pregnant human urine samples analysed by liquid chromatography-mass spectrometry (LC-MS). Morning urine samples were collected over two consecutive days from 42 volunteers and associated food consumption was recorded for the 24 h prior to the sample. Spearman’s rho non-parametric test for correlation was used to assess the data. Levels of DON did not differ significantly between day 1 (mean 29.7 ng/mL urine or 40.1 ng DON/mg creatinine) and day 2 (mean 28.7 ng/mL urine or 38.8 ng DON/mg creatinine ng/mL/day) urine samples. The only significant positive correlation was found between total ng DON/mg creatinine and parity (rho = 0.307, n = 42, p < 0.005 two-tailed) and total ng DON/mg creatinine with baked goods on day 1 (rho = 0.532, n = 42, p < 0.0005 two-tailed). This study provides data on the DON levels in pregnancy in this suburban population and reassurance that those levels are within acceptable limits. Full article

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Open AccessArticle

Pentahydroxyscirpene—Producing Strains, Formation In Planta, and Natural Occurrence

by Elisabeth Varga, Gerlinde Wiesenberger, Philipp Fruhmann, Alexandra Malachová, Thomas Svoboda, Marc Lemmens, Gerhard Adam and Franz Berthiller

Toxins 2016, 8(10), 295; https://doi.org/10.3390/toxins8100295 - 14 Oct 2016

Cited by 1 | Viewed by 4451

Abstract

Trichothecenes are a class of structurally diverse mycotoxins with more than 200 naturally occurring compounds. Previously, a new compound, pentahydroxyscirpene (PHS), was reported as a byproduct of a nivalenol producing Fusarium strain, IFA189. PHS contains a hydroxy group at C-8 instead of the [...] Read more.

Trichothecenes are a class of structurally diverse mycotoxins with more than 200 naturally occurring compounds. Previously, a new compound, pentahydroxyscirpene (PHS), was reported as a byproduct of a nivalenol producing Fusarium strain, IFA189. PHS contains a hydroxy group at C-8 instead of the keto group of type B trichothecenes. In this work, we demonstrate that IFA189 belongs to the species Fusarium kyushuense using molecular tools. Production of PHS in vitro was also observed for several isolates of other Fusarium species producing nivalenol. Furthermore, we report the formation of 4-acetyl-PHS by F. kyushuense on inoculated rice. Wheat ears of the variety Remus were infected with IFA189 and the in planta production of PHS was confirmed. Natural occurrence of PHS was verified in barley samples from the Czech Republic using a liquid chromatographic-tandem mass spectrometric method validated for this purpose. Toxicity of PHS to wheat ribosomes was evaluated with a coupled in vitro transcription and translation assay, which showed that PHS inhibits protein biosynthesis slightly less than nivalenol and deoxynivalenol. Full article

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Open AccessArticle

Susceptibility of Broiler Chickens to Coccidiosis When Fed Subclinical Doses of Deoxynivalenol and Fumonisins—Special Emphasis on the Immunological Response and the Mycotoxin Interaction

by Bertrand Grenier, Ilse Dohnal, Revathi Shanmugasundaram, Susan D. Eicher, Ramesh K. Selvaraj, Gerd Schatzmayr and Todd J. Applegate

Toxins 2016, 8(8), 231; https://doi.org/10.3390/toxins8080231 - 27 Jul 2016

Cited by 43 | Viewed by 8517

Abstract

Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species in livestock diets. The effect of subclinical doses of mycotoxins in chickens is largely unknown, and in particular the susceptibility of birds to pathogenic challenge when fed these [...] Read more.

Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species in livestock diets. The effect of subclinical doses of mycotoxins in chickens is largely unknown, and in particular the susceptibility of birds to pathogenic challenge when fed these fungal metabolites. Therefore, the present study reports the effects of DON and FB on chickens challenged with Eimeria spp, responsible for coccidiosis. Broilers were fed diets from hatch to day 20, containing no mycotoxins, 1.5 mg DON/kg, 20 mg FB/kg, or both toxins (12 pens/diet; 7 birds/pen). At day 14, six pens of birds per diet (half of the birds) were challenged with a 25×-recommended dose of coccidial vaccine, and all birds (challenged and unchallenged) were sampled 6 days later. As expected, performance of birds was strongly affected by the coccidial challenge. Ingestion of mycotoxins did not further affect the growth but repartitioned the rate of reduction (between the fraction due to the change in maintenance and feed efficiency), and reduced apparent nitrogen digestibility. Intestinal lesions and number of oocysts in the jejunal mucosa and feces of challenged birds were more frequent and intense in the birds fed mycotoxins than in birds fed control feed. The upregulation of cytokines (interleukin (IL) IL-1β, IL-6, IL-8 and IL-10) following coccidial infection was higher in the jejunum of birds fed mycotoxins. Further, the higher intestinal immune response was associated with a higher percentage of T lymphocytes CD4⁺CD25⁺, also called T_regs, observed in the cecal tonsils of challenged birds fed mycotoxins. Interestingly, the increase in FB biomarker of exposure (sphinganine/sphingosine ratio in serum and liver) suggested a higher absorption and bioavailability of FB in challenged birds. The interaction of DON and FB was very dependent on the endpoint assessed, with three endpoints reporting antagonism, nine additivity, and two synergism. In conclusion, subclinical doses of DON and FB showed little effects in unchallenged chickens, but seem to result in metabolic and immunologic disturbances that amplify the severity of coccidiosis. Full article

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Open AccessArticle

Identification of Pathogenic Fusarium spp. Causing Maize Ear Rot and Potential Mycotoxin Production in China

by Canxing Duan, Zihui Qin, Zhihuan Yang, Weixi Li, Suli Sun, Zhendong Zhu and Xiaoming Wang

Toxins 2016, 8(6), 186; https://doi.org/10.3390/toxins8060186 - 21 Jun 2016

Cited by 78 | Viewed by 8215

Abstract

Ear rot is a serious disease that affects maize yield and grain quality worldwide. The mycotoxins are often hazardous to humans and livestock. In samples collected in China between 2009 and 2014, Fusarium verticillioides and F. graminearum species complex were the dominant fungi [...] Read more.

Ear rot is a serious disease that affects maize yield and grain quality worldwide. The mycotoxins are often hazardous to humans and livestock. In samples collected in China between 2009 and 2014, Fusarium verticillioides and F. graminearum species complex were the dominant fungi causing ear rot. According to the TEF-1α gene sequence, F. graminearum species complex in China included three independent species: F. graminearum, F. meridionale, and F. boothii. The key gene FUM1 responsible for the biosynthesis of fumonisin was detected in all 82 F. verticillioides isolates. Among these, 57 isolates mainly produced fumonisin B₁, ranging from 2.52 to 18,416.44 µg/g for each gram of dry hyphal weight, in vitro. Three different toxigenic chemotypes were detected among 78 F. graminearum species complex: 15-ADON, NIV and 15-ADON+NIV. Sixty and 16 isolates represented the 15-ADON and NIV chemotypes, respectively; two isolates carried both 15-ADON and NIV-producing segments. All the isolates carrying NIV-specific segment were F. meridionale. The in vitro production of 15-ADON, 3-ADON, DON, and ZEN varied from 5.43 to 81,539.49; 6.04 to 19,590.61; 13.35 to 19,795.33; and 1.77 to 430.24 µg/g of dry hyphal weight, respectively. Altogether, our present data demonstrate potential main mycotoxin production of dominant pathogenic Fusarium in China. Full article

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Open AccessArticle

The Response of Selected Triticum spp. Genotypes with Different Ploidy Levels to Head Blight Caused by Fusarium culmorum (W.G.Smith) Sacc.

by Marian Wiwart, Elżbieta Suchowilska, Wolfang Kandler, Michael Sulyok, Urszula Wachowska and Rudolf Krska

Toxins 2016, 8(4), 112; https://doi.org/10.3390/toxins8040112 - 15 Apr 2016

Cited by 12 | Viewed by 5175

Abstract

Several cultivars and pure lines of Triticum monococcum, T. dicoccon, T. polonicum, T. spelta and T. aestivum were inoculated with Fusarium culmorum, the causal agent of Fusarium head blight in wheat. During the three-year study, the infection decreased the [...] Read more.

Several cultivars and pure lines of Triticum monococcum, T. dicoccon, T. polonicum, T. spelta and T. aestivum were inoculated with Fusarium culmorum, the causal agent of Fusarium head blight in wheat. During the three-year study, the infection decreased the values of the analyzed yield components: spike weight (by 5.6% to 15.8%), number of kernels per spike (by 2.8% to 11.8%) and one kernel weight (by 8.4% to 10.7%). T. spelta was characterized by the weakest average response to infection. The grain from inoculated spikes contained significantly higher concentrations of deoxynivalenol (DON) and its 3-β-d-glucoside (D3G) than control grain. The D3G/DON ratio ranged from 11.4% to 21.4% in control grain and from 8.1% to 11.6% in inoculated grain. The lowest levels of mycotoxins were found in spelt, and the highest in T. polonicum lines and Kamut. PCA revealed that the grain of T. polonicum was characterized by an entirely different mycotoxin profile. The weakest response to F. culmorum infections was noted in T. spelta, and the strongest response in T. polonicum breeding lines and Kamut. Full article

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Open AccessReview

Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects

by Marie-Caroline Smith, Stéphanie Madec, Emmanuel Coton and Nolwenn Hymery

Toxins 2016, 8(4), 94; https://doi.org/10.3390/toxins8040094 - 26 Mar 2016

Cited by 436 | Viewed by 18631

Abstract

Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural [...] Read more.

Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. Full article

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Open AccessArticle

Fumonisin B₁ (FB₁) Induces Lamellar Separation and Alters Sphingolipid Metabolism of In Vitro Cultured Hoof Explants

by Nicole Reisinger, Ilse Dohnal, Veronika Nagl, Simone Schaumberger, Gerd Schatzmayr and Elisabeth Mayer

Toxins 2016, 8(4), 89; https://doi.org/10.3390/toxins8040089 - 24 Mar 2016

Cited by 12 | Viewed by 5813

Abstract

One of the most important hoof diseases is laminitis. Yet, the pathology of laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins, toxic secondary metabolites of fungi, might contribute to [...] Read more.

One of the most important hoof diseases is laminitis. Yet, the pathology of laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins, toxic secondary metabolites of fungi, might contribute to the onset of laminitis. In this respect, fumonsins are of special interest since horses are regarded as species most susceptible to this group of mycotoxins. The aim of our study was to investigate the influence of fumonisin B₁ (FB₁) on primary isolated epidermal and dermal hoof cells, as well as on the lamellar tissue integrity and sphingolipid metabolism of hoof explants in vitro. There was no effect of FB₁ at any concentration on dermal or epidermal cells. However, FB₁ significantly reduced the separation force of explants after 24 h of incubation. The Sa/So ratio was significantly increased in supernatants of explants incubated with FB₁ (2.5–10 µg/mL) after 24 h. Observed effects on Sa/So ratio were linked to significantly increased sphinganine concentrations. Our study showed that FB₁ impairs the sphingolipid metabolism of explants and reduces lamellar integrity at non-cytotoxic concentrations. FB₁ might, therefore, affect hoof health. Further in vitro and in vivo studies are necessary to elucidate the effects of FB₁ on the equine hoof in more detail. Full article

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Open AccessArticle

Gastrointestinal Degradation of Fumonisin B₁ by Carboxylesterase FumD Prevents Fumonisin Induced Alteration of Sphingolipid Metabolism in Turkey and Swine

by Sabine Masching, Karin Naehrer, Heidi-Elisabeth Schwartz-Zimmermann, Mihai Sărăndan, Simone Schaumberger, Ilse Dohnal, Veronika Nagl and Dian Schatzmayr

Toxins 2016, 8(3), 84; https://doi.org/10.3390/toxins8030084 - 21 Mar 2016

Cited by 62 | Viewed by 8244

Abstract

The mycotoxin fumonisin B₁ (FB₁) is a frequent contaminant of feed and causes various adverse health effects in domestic animals. Hence, effective strategies are needed to prevent the impact of fumonisins on livestock productivity. Here we evaluated the capability of [...] Read more.

The mycotoxin fumonisin B₁ (FB₁) is a frequent contaminant of feed and causes various adverse health effects in domestic animals. Hence, effective strategies are needed to prevent the impact of fumonisins on livestock productivity. Here we evaluated the capability of the fumonisin carboxylesterase FumD to degrade FB₁ to its less toxic metabolite hydrolyzed FB₁ (HFB₁) in the gastrointestinal tract of turkeys and pigs. First, an ex vivo pig model was used to examine the activity of FumD under digestive conditions. Within 2 h of incubation with FumD, FB₁ was completely degraded to HFB₁ in the duodenum and jejunum, respectively. To test the efficacy of the commercial application of FumD (FUMzyme) in vivo, female turkeys (n = 5) received either basal feed (CON), fumonisin-contaminated feed (15 mg/kg FB₁+FB₂; FB) or fumonisin-contaminated feed supplemented with FUMzyme (15 U/kg; FB+FUMzyme) for 14 days ad libitum. Addition of FUMzyme resulted in significantly decreased levels of FB₁ in excreta, whereas HFB₁ concentrations were significantly increased. Compared to the FB group (0.24 ± 0.02), the mean serum sphinganine-to-sphingosine (Sa/So) ratio was significantly reduced in the FB+FUMzyme group (0.19 ± 0.02), thus resembling values of the CON group (0.16 ± 0.02). Similarly, exposure of piglets (n = 10) to 2 mg/kg FB₁+FB₂ for 42 days caused significantly elevated serum Sa/So ratios (0.39 ± 0.15) compared to the CON group (0.14 ± 0.01). Supplementation with FUMzyme (60 U/kg) resulted in gastrointestinal degradation of FB₁ and unaffected Sa/So ratios (0.16 ± 0.02). Thus, the carboxylesterase FumD represents an effective strategy to detoxify FB₁ in the digestive tract of turkeys and pigs. Full article

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Open AccessArticle

Acetylated Deoxynivalenol Generates Differences of Gene Expression that Discriminate Trichothecene Toxicity

by Tadahiro Suzuki and Yumiko Iwahashi

Toxins 2016, 8(2), 42; https://doi.org/10.3390/toxins8020042 - 6 Feb 2016

Cited by 6 | Viewed by 5005

Abstract

Deoxynivalenol (DON), which is a toxic secondary metabolite generated by Fusarium species, is synthesized through two separate acetylation pathways. Both acetylation derivatives, 3-acetyl-DON (3ADON) and 15-acetyl-DON (15ADON), also contaminate grain and corn widely. These derivatives are deacetylated via a variety of processes after [...] Read more.

Deoxynivalenol (DON), which is a toxic secondary metabolite generated by Fusarium species, is synthesized through two separate acetylation pathways. Both acetylation derivatives, 3-acetyl-DON (3ADON) and 15-acetyl-DON (15ADON), also contaminate grain and corn widely. These derivatives are deacetylated via a variety of processes after ingestion, so it has been suggested that they have the same toxicity as DON. However, in the intestinal entry region such as the duodenum, the derivatives might come into contact with intestinal epithelium cells because metabolism by microflora or import into the body has not progressed. Therefore, the differences of toxicity between DON and these derivatives need to be investigated. Here, we observed gene expression changes in the yeast pdr5Δ mutant strain under concentration-dependent mycotoxin exposure conditions. 15ADON exposure induced significant gene expression changes and DON exposure generally had a similar but smaller effect. However, the glucose transporter genes HXT2 and HXT4 showed converse trends. 3ADON also induced a different expression trend in these genes than DON and 15ADON. These differences in gene expression suggest that DON and its derivatives have different effects on cells. Full article

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2015

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3007 KiB

Open AccessArticle

Does Dietary Deoxynivalenol Modulate the Acute Phase Reaction in Endotoxaemic Pigs?—Lessons from Clinical Signs, White Blood Cell Counts, and TNF-Alpha

by Tanja Tesch, Erik Bannert, Jeannette Kluess, Jana Frahm, Susanne Kersten, Gerhard Breves, Lydia Renner, Stefan Kahlert, Hermann-Josef Rothkötter and Sven Dänicke

Toxins 2016, 8(1), 3; https://doi.org/10.3390/toxins8010003 - 23 Dec 2015

Cited by 14 | Viewed by 6235

Abstract

We studied the interaction between deoxynivalenol (DON)-feeding and a subsequent pre- and post-hepatic immune stimulus with the hypothesis that the liver differently mediates the acute phase reaction (APR) in pigs. Barrows (n = 44) were divided into a DON-(4.59 mg DON/kg feed) [...] Read more.

We studied the interaction between deoxynivalenol (DON)-feeding and a subsequent pre- and post-hepatic immune stimulus with the hypothesis that the liver differently mediates the acute phase reaction (APR) in pigs. Barrows (n = 44) were divided into a DON-(4.59 mg DON/kg feed) and a control-diet group, surgically equipped with permanent catheters pre- (V. portae hepatis) and post-hepatic (V. jugularis interna) and infused either with 0.9% NaCl or LPS (7.5 µg/kg BW). Thus, combination of diet (CON vs. DON) and infusion (CON vs. LPS, jugular vs. portal) created six groups: CON_CON_jug.-CON_por., CON_CON_jug.-LPS_por., CON_LPS_jug.-CON_por., DON_CON_jug.-CON_por., DON_CON_jug.-LPS_por., DON_LPS_jug.-CON_por.. Blood samples were taken at −30, 15, 30, 45, 60, 75, 90, 120, 150, 180 min relative to infusion and analyzed for leukocytes and TNF-alpha. Concurrently, clinical signs were scored and body temperature measured during the same period. LPS as such induced a dramatic rise in TNF-alpha (p < 0.001), hyperthermia (p < 0.01), and severe leukopenia (p < 0.001). In CON-fed pigs, an earlier return to physiological base levels was observed for the clinical complex, starting at 120 min post infusionem (p < 0.05) and persisting until 180 min. DON_LPS_jug.-CON_por. resulted in a lower temperature rise (p = 0.08) compared to CON_LPS_jug.-CON_por.. In conclusion, APR resulting from a post-hepatic immune stimulus was altered by chronic DON-feeding. Full article

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Open AccessArticle

Metabolism of Deoxynivalenol and Deepoxy-Deoxynivalenol in Broiler Chickens, Pullets, Roosters and Turkeys

by Heidi E. Schwartz-Zimmermann, Philipp Fruhmann, Sven Dänicke, Gerlinde Wiesenberger, Sylvia Caha, Julia Weber and Franz Berthiller

Toxins 2015, 7(11), 4706-4729; https://doi.org/10.3390/toxins7114706 - 12 Nov 2015

Cited by 48 | Viewed by 7491

Abstract

Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens [...] Read more.

Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens and turkeys was developed and validated. To this end, DOM-3-sulfate was chemically synthesized and characterized by NMR and LC-HR-MS/MS measurements. Application of the method to excreta and chyme samples of four feeding trials with turkeys, chickens, pullets, and roosters confirmed DON-3-sulfate as the major DON metabolite in all poultry species studied. Analogously to DON-3-sulfate, DOM-3-sulfate was formed after oral administration of DOM both in turkeys and in chickens. In addition, pullets and roosters metabolized DON into DOM-3-sulfate. In vitro transcription/translation assays revealed DOM-3-sulfate to be 2000 times less toxic on the ribosome than DON. Biological recoveries of DON and DOM orally administered to broiler chickens, turkeys, and pullets were 74%–106% (chickens), 51%–72% (roosters), and 131%–151% (pullets). In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60. This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine. Full article

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Open AccessArticle

Studies on the Bioavailability of Deoxynivalenol (DON) and DON Sulfonate (DONS) 1, 2, and 3 in Pigs Fed with Sodium Sulfite-Treated DON-Contaminated Maize

by Marleen Paulick, Janine Winkler, Susanne Kersten, Dian Schatzmayr, Heidi Elisabeth Schwartz-Zimmermann and Sven Dänicke

Toxins 2015, 7(11), 4622-4644; https://doi.org/10.3390/toxins7114622 - 5 Nov 2015

Cited by 16 | Viewed by 5413

Abstract

Deoxynivalenol (DON) exposure of pigs might cause serious problems when critical dietary toxin concentrations are exceeded. As DON contamination of agricultural crops cannot be completely prevented, detoxification measures are needed. Wet preservation with sodium sulfite resulted in a significant DON reduction of naturally-contaminated [...] Read more.

Deoxynivalenol (DON) exposure of pigs might cause serious problems when critical dietary toxin concentrations are exceeded. As DON contamination of agricultural crops cannot be completely prevented, detoxification measures are needed. Wet preservation with sodium sulfite resulted in a significant DON reduction of naturally-contaminated maize in previous experiments. The preserved material had a characteristic DON sulfonates (DONS) pattern. DONS is known to be less toxic than DON but its stability was shown to depend on pH, which gives rise to the question if a back-conversion to DON occurs in vivo. Therefore, the toxicokinetics and bioavailability of DON and DONS were studied in pigs. After the administration of a single oral or intravenous bolus of DON or DONS, serial blood samples were collected and subsequently analyzed. DONS was not detectable after oral administration of DONS mixtures. The results showed further that the bioavailability of DONS as DON in pigs fed maize preserved wet with sodium sulfite was significantly decreased compared to untreated control maize (DON), indicating that DONS obviously did not convert back to DON to a large extent in vivo. Moreover, the fact that DONS was not detectable in systemic blood requires further investigations regarding their ingestive and/or metabolic fate. Full article

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Open AccessArticle

Detection of N-(1-deoxy-d-fructos-1-yl) Fumonisins B₂ and B₃ in Corn by High-Resolution LC-Orbitrap MS

by Yosuke Matsuo, Kentaro Takahara, Yuki Sago, Masayo Kushiro, Hitoshi Nagashima and Hiroyuki Nakagawa

Toxins 2015, 7(9), 3700-3714; https://doi.org/10.3390/toxins7093700 - 16 Sep 2015

Cited by 12 | Viewed by 5725

Abstract

The existence of glucose conjugates of fumonisin B₂ (FB₂) and fumonisin B₃ (FB₃) in corn powder was confirmed for the first time. These “bound-fumonisins” (FB₂ and FB₃ bound to glucose) were identified as N-(1-deoxy-d-fructos-1-yl) [...] Read more.

The existence of glucose conjugates of fumonisin B₂ (FB₂) and fumonisin B₃ (FB₃) in corn powder was confirmed for the first time. These “bound-fumonisins” (FB₂ and FB₃ bound to glucose) were identified as N-(1-deoxy-d-fructos-1-yl) fumonisin B₂ (NDfrc-FB₂) and N-(1-deoxy-d-fructos-1-yl) fumonisin B₃ (NDfrc-FB₃) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB₂ and NDfrc-FB₃ with the o-phthalaldehyde (OPA) reagent also supported that d-glucose binding to FB₂ and FB₃ molecules occurred to their primary amine residues. Full article

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Graphical abstract

256 KiB

Open AccessArticle

Zearalenone in the Intestinal Tissues of Immature Gilts Exposed per os to Mycotoxins

by Łukasz Zielonka, Agnieszka Waśkiewicz, Monika Beszterda, Marian Kostecki, Michał Dąbrowski, Kazimierz Obremski, Piotr Goliński and Maciej Gajęcki

Toxins 2015, 7(8), 3210-3223; https://doi.org/10.3390/toxins7083210 - 18 Aug 2015

Cited by 35 | Viewed by 5674

Abstract

Zearalenone and its metabolites, α-zearalenol and β-zearalenol, demonstrate estradiol-like activity and disrupt physiological functions in animals. This article evaluates the carryover of zearalenone and its selected metabolites from the digesta to intestinal walls (along the entire intestines) in pre-pubertal gilts exposed to low [...] Read more.

Zearalenone and its metabolites, α-zearalenol and β-zearalenol, demonstrate estradiol-like activity and disrupt physiological functions in animals. This article evaluates the carryover of zearalenone and its selected metabolites from the digesta to intestinal walls (along the entire intestines) in pre-pubertal gilts exposed to low doses of zearalenone over long periods of time. The term “carryover” describes the transfer of mycotoxins from feed to edible tissues, and it was used to assess the risk of mycotoxin exposure for consumers. The experimental gilts with body weight of up to 25 kg were per os administered zearalenone at a daily dose of 40 μg/kg BW (Group E, n = 18) or placebo (Group C, n = 21) over a period of 42 days. In the first weeks of exposure, the highest values of the carryover factor were noted in the duodenum and the jejunum. In animals receiving pure zearalenone, the presence of metabolites was not determined in intestinal tissues. In the last three weeks of the experiment, very high values of the carryover factor were observed in the duodenum and the descending colon. The results of the study indicate that in animals exposed to subclinical doses of zearalenone, the carryover factor could be determined by the distribution and expression of estrogen receptor beta. Full article

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Open AccessArticle

Deoxynivalenol Impairs Weight Gain and Affects Markers of Gut Health after Low-Dose, Short-Term Exposure of Growing Pigs

by Arash Alizadeh, Saskia Braber, Peyman Akbari, Johan Garssen and Johanna Fink-Gremmels

Toxins 2015, 7(6), 2071-2095; https://doi.org/10.3390/toxins7062071 - 9 Jun 2015

Cited by 88 | Viewed by 9854

Abstract

Deoxynivalenol (DON) is one of the major mycotoxins produced by Fusarium fungi, and exposure to this mycotoxin requires an assessment of the potential adverse effects, even at low toxin levels. The aim of this study was to investigate the effects of a short-term, [...] Read more.

Deoxynivalenol (DON) is one of the major mycotoxins produced by Fusarium fungi, and exposure to this mycotoxin requires an assessment of the potential adverse effects, even at low toxin levels. The aim of this study was to investigate the effects of a short-term, low-dose DON exposure on various gut health parameters in pigs. Piglets received a commercial feed or the same feed contaminated with DON (0.9 mg/kg feed) for 10 days, and two hours after a DON bolus (0.28 mg/kg BW), weight gain was determined and samples of different segments of the intestine were collected. Even the selected low dose of DON in the diet negatively affected weight gain and induced histomorphological alterations in the duodenum and jejunum. The mRNA expression of different tight junction (TJ) proteins, especially occludin, of inflammatory markers, like interleukin-1 beta and interleukin-10 and the oxidative stress marker heme-oxigenase1, were affected along the intestine by low levels of DON in the diet. Taken together, our results indicate that even after low-level exposure to DON, which has been generally considered as acceptable in animal feeds, clinically-relevant changes are measurable in markers of gut health and integrity. Full article

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362 KiB

Open AccessArticle

Food Contaminant Zearalenone and Its Metabolites Affect Cytokine Synthesis and Intestinal Epithelial Integrity of Porcine Cells

by Daniela E. Marin, Monica Motiu and Ionelia Taranu

Toxins 2015, 7(6), 1979-1988; https://doi.org/10.3390/toxins7061979 - 29 May 2015

Cited by 51 | Viewed by 7814

Abstract

The intestinal epithelium is the first barrier against food contaminants. Zearalenone (ZEN) is an estrogenic mycotoxin that was identified as a common contaminant of cereal grains and food and feedstuffs. In the present study, we have investigated the in vitro effects of ZEN [...] Read more.

The intestinal epithelium is the first barrier against food contaminants. Zearalenone (ZEN) is an estrogenic mycotoxin that was identified as a common contaminant of cereal grains and food and feedstuffs. In the present study, we have investigated the in vitro effects of ZEN and some of its metabolites (α-ZOL, β-ZOL) in concentrations of 10–100 µM on a swine epithelial cell line: Intestinal porcine epithelial cells (IPEC-1). We demonstrated that both ZEN metabolites were more toxic for IPEC cells as resulted from the XTT test, while for doses lower than 10 µM, only β-ZOL showed a more pronounced cytotoxicity versus epithelial cells as resulted from neutral red assay. ZEN has no effect on TER values, while α-ZOL significantly decreased the TER values, starting with day 4 of treatment. β-ZOL had a dual effect, firstly it induced a significant increase of TER, and then, starting on day 6, it induced a dramatic decrease of TER values as compared with on day 0. Concerning the cytokine synthesis, our results showed that ZEN has a tendency to increase the synthesis of IL-8 and IL-10. By contrast, α- and β-ZOL decreased the expression of both IL-8 and IL-10, in a dose dependent manner. In conclusion, our results showed that ZEN and its metabolites differently affected porcine intestinal cell viability, transepithelial resistance and cytokine synthesis with important implication for gut health. Full article

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Open AccessArticle

Nivalenol Has a Greater Impact than Deoxynivalenol on Pig Jejunum Mucosa in Vitro on Explants and in Vivo on Intestinal Loops

by Sophal Cheat, Juliana R. Gerez, Juliette Cognié, Imourana Alassane-Kpembi, Ana Paula F. L. Bracarense, Isabelle Raymond-Letron, Isabelle P. Oswald and Martine Kolf-Clauw

Toxins 2015, 7(6), 1945-1961; https://doi.org/10.3390/toxins7061945 - 29 May 2015

Cited by 56 | Viewed by 8186

Abstract

The mycotoxins deoxynivalenol (DON) and nivalenol (NIV), worldwide cereal contaminants, raise concerns for animal and human gut health, following contaminated food or feed ingestion. The impact of DON and NIV on intestinal mucosa was investigated after acute exposure, in vitro and in vivo [...] Read more.

The mycotoxins deoxynivalenol (DON) and nivalenol (NIV), worldwide cereal contaminants, raise concerns for animal and human gut health, following contaminated food or feed ingestion. The impact of DON and NIV on intestinal mucosa was investigated after acute exposure, in vitro and in vivo. The histological changes induced by DON and NIV were analyzed after four-hour exposure on pig jejunum explants and loops, two alternative models. On explants, dose-dependent increases in the histological changes were induced by DON and NIV, with a two-fold increase in lesion severity at 10 µM NIV. On loops, NIV had a greater impact on the mucosa than DON. The overall proliferative cells showed 30% and 13% decrease after NIV and DON exposure, respectively, and NIV increased the proliferative index of crypt enterocytes. NIV also increased apoptosis at the top of villi and reduced by almost half the proliferative/apoptotic cell ratio. Lamina propria cells (mainly immune cells) were more sensitive than enterocytes (epithelial cells) to apoptosis induced by NIV. Our results demonstrate a greater impact of NIV than DON on the intestinal mucosa, both in vitro and in vivo, and highlight the need of a specific hazard characterization for NIV risk assessment. Full article

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521 KiB

Open AccessArticle

Effects of Wheat Naturally Contaminated with Fusarium Mycotoxins on Growth Performance and Selected Health Indices of Red Tilapia (Oreochromis niloticus × O. mossambicus)

by Siriporn Tola, Dominique P. Bureau, Jamie M. Hooft, Frederick W. H. Beamish, Michael Sulyok, Rudolf Krska, Pedro Encarnação and Rakpong Petkam

Toxins 2015, 7(6), 1929-1944; https://doi.org/10.3390/toxins7061929 - 29 May 2015

Cited by 28 | Viewed by 7005

Abstract

An 8-week feeding trial was conducted to examine effects of wheat naturally contaminated with Fusarium mycotoxins (deoxynivalenol, DON 41 mg·kg⁻¹) on growth performance and selected health indices of red tilapia (Oreochromis niloticus × O. mossambicus; initial weight = [...] Read more.

An 8-week feeding trial was conducted to examine effects of wheat naturally contaminated with Fusarium mycotoxins (deoxynivalenol, DON 41 mg·kg⁻¹) on growth performance and selected health indices of red tilapia (Oreochromis niloticus × O. mossambicus; initial weight = 4.3 g/fish). Five experimental diets were formulated by replacement of clean wheat with naturally contaminated wheat resulting in graded levels of DON and zearalenone (ZEN) (Diet 1 0.07/0.01, Diet 2 0.31/0.09, Diet 3 0.50/0.21, Diet 4 0.92/0.37 and Diet 5 1.15/0.98 mg·kg⁻¹). Groups of 50 fish were randomly allocated into each of 20 aquaria and fed to near-satiety for eight weeks. Growth rate, feed intake and feed efficiency of fish fed the experimental diets decreased linearly with increasing levels of Fusarium mycotoxins (p < 0.05). Although growth depression was associated with feeding diets naturally contaminated with Fusarium mycotoxins, especially DON, no biochemical and histopathological parameters measured in blood and liver appeared affected by Fusarium mycotoxin concentrations of diets (p > 0.05). Though there was no clear evidence of overt DON toxicity to red tilapia, it is recommended that feed ingredients should be screened for Fusarium mycotoxin contamination to ensure optimal growth performance. Full article

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Open AccessArticle

Preliminary Estimation of Deoxynivalenol Excretion through a 24 h Pilot Study

by Yelko Rodríguez-Carrasco, Jordi Mañes, Houda Berrada and Guillermina Font

Toxins 2015, 7(3), 705-718; https://doi.org/10.3390/toxins7030705 - 25 Feb 2015

Cited by 26 | Viewed by 5865

Abstract

A duplicate diet study was designed to explore the occurrence of 15 Fusarium mycotoxins in the 24 h-diet consumed by one volunteer as well as the levels of mycotoxins in his 24 h-collected urine. The employed methodology involved solvent extraction at high ionic [...] Read more.

A duplicate diet study was designed to explore the occurrence of 15 Fusarium mycotoxins in the 24 h-diet consumed by one volunteer as well as the levels of mycotoxins in his 24 h-collected urine. The employed methodology involved solvent extraction at high ionic strength followed by dispersive solid phase extraction and gas chromatography determination coupled to mass spectrometry in tandem. Satisfactory results in method performance were achieved. The method’s accuracy was in a range of 68%–108%, with intra-day relative standard deviation and inter-day relative standard deviation lower than 12% and 15%, respectively. The limits of quantitation ranged from 0.1 to 8 µg/Kg. The matrix effect was evaluated and matrix-matched calibrations were used for quantitation. Only deoxynivalenol (DON) was quantified in both food and urine samples. A total DON daily intake amounted to 49.2 ± 5.6 µg whereas DON daily excretion of 35.2 ± 4.3 µg was determined. DON daily intake represented 68.3% of the established DON provisional maximum tolerable daily intake (PMTDI). Valuable preliminary information was obtained as regards DON excretion and needs to be confirmed in large-scale monitoring studies. Full article

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718 KiB

Open AccessCommunication

Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

by Gina Manda, Mihaela Andreea Mocanu, Daniela Eliza Marin and Ionelia Taranu

Toxins 2015, 7(2), 593-603; https://doi.org/10.3390/toxins7020593 - 16 Feb 2015

Cited by 21 | Viewed by 6767

Abstract

Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower [...] Read more.

Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37–1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics. Full article

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321 KiB

Open AccessCommunication

Chronic Exposure to Deoxynivalenol Has No Influence on the Oral Bioavailability of Fumonisin B₁ in Broiler Chickens

by Gunther Antonissen, Mathias Devreese, Filip Van Immerseel, Siegrid De Baere, Sabine Hessenberger, An Martel and Siska Croubels

Toxins 2015, 7(2), 560-571; https://doi.org/10.3390/toxins7020560 - 16 Feb 2015

Cited by 15 | Viewed by 6270

Abstract

Both deoxynivalenol (DON) and fumonisin B₁ (FB₁) are common contaminants of feed. Fumonisins (FBs) in general have a very limited oral bioavailability in healthy animals. Previous studies have demonstrated that chronic exposure to DON impairs the intestinal barrier function and [...] Read more.

Both deoxynivalenol (DON) and fumonisin B₁ (FB₁) are common contaminants of feed. Fumonisins (FBs) in general have a very limited oral bioavailability in healthy animals. Previous studies have demonstrated that chronic exposure to DON impairs the intestinal barrier function and integrity, by affecting the intestinal surface area and function of the tight junctions. This might influence the oral bioavailability of FB₁, and possibly lead to altered toxicity of this mycotoxin. A toxicokinetic study was performed with two groups of 6 broiler chickens, which were all administered an oral bolus of 2.5 mg FBs/kg BW after three-week exposure to either uncontaminated feed (group 1) or feed contaminated with 3.12 mg DON/kg feed (group 2). No significant differences in toxicokinetic parameters of FB₁ could be demonstrated between the groups. Also, no increased or decreased body exposure to FB₁ was observed, since the relative oral bioavailability of FB₁ after chronic DON exposure was 92.2%. Full article

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