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Toxins
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Recent Advances in Ochratoxins Research
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Recent Advances in Ochratoxins Research

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (31 October 2013) | Viewed by 94152

Special Issue Editors

Prof. Dr. Annie Pfohl-Leszkowicz

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Guest Editor
Department Bioprocess & Microbial Systems, Laboratory Chemical Engineering, INP/ENSA Toulouse, University of Toulouse, UMR 5503 CNRS/INPT/UPS, Auzeville-Tolosane 31320, France
Interests: mycotoxin; ochratoxin; fumonisin; zearalenone; biomarker; risk evaluation; environmental toxicology; polycyclic aromatic compounds; genotoxicity; DNA adduct; balkan endemic nephropathy; kidney cancer; biotransformation
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Richard A. Manderville

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Guest Editor
Department of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
Interests: DNA damage by phenolic toxins including ochratoxin A; Modified DNA bases as fluorescent probes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ochratoxin A (OTA) is a naturally occurring chlorophenolic fungal toxin that contaminates a wide range of food products (cereals, coffee, cocoa, bean, peanut, spice, meat) and poses a serious risk for human and animal health, that includes: renal toxicity, reprotoxicity, neurotoxicity, immunotoxicity and mutagenicity. To date, it is one of the most potent renal carcinogens in rodents ever studied by the National Cancer Institute/National Toxicological Program. The available evidence suggests that OTA is a genotoxic carcinogen by induction of oxidative DNA lesions coupled with direct DNA adducts following bioactivation.

Harmful effects of OTA can be potentiated by possible synergistic action with other mycotoxins or contaminants. The existence of these synergies makes assessment of the exact role of OTA in human and animal pathologies far more complex, especially when it comes to long-term perspective. Continuous monitoring for the presence of OTA is imperative, as is the adequate response in term of legislative measures and good agricultural practices.

This special issue is devoted to recent advances in OTA research, through both research articles and comprehensive reviews focusing on animal and human toxicity, risk assessment, monitoring strategies (development of biomarkers), detoxification strategies for mitigation both animal and human health risk, and synergistic impact between OTA and other compounds.

Prof. Dr. Annie Pfohl-Leszkowicz
Prof. Dr. Richard A. Manderville
Guest Editors

 

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs).

Keywords

  • ochratoxins
  • mycotoxins
  • occurrence
  • biosensor
  • intake
  • biomarkers
  • mechanism of action
  • synergy
  • mitigation
  • biotransformation
  • risk assessment
  • food/feed safety
  • Penicillium
  • Aspergillus

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Related Special Issue

Published Papers (10 papers)

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Research

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959 KiB  
Article
In Vitro Glucuronidation of Ochratoxin A by Rat Liver Microsomes
by Zheng Han, Emmanuel K. Tangni, José Diana Di Mavungu, Lynn Vanhaecke, Sarah De Saeger, Aibo Wu and Alfons Callebaut
Toxins 2013, 5(12), 2671-2685; https://doi.org/10.3390/toxins5122671 - 18 Dec 2013
Cited by 21 | Viewed by 8647
Abstract
Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid [...] Read more.
Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), UHPLC-Orbitrap-high resolution mass spectrometry (HRMS) and liquid chromatography-multiple stage mass spectrometry (LC-MSn) were utilized to investigate the metabolic profile of OTA in rat liver microsomes. Three conjugated products of OTA corresponding to amino-, phenol- and acyl-glucuronides were identified, and the related structures were confirmed by hydrolysis with β-glucuronidase. Moreover, OTA methyl ester, OTα and OTα-glucuronide were also found in the reaction solution. Based on these results, an in vitro metabolic pathway of OTA has been proposed for the first time. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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327 KiB  
Article
Impact of pH on the Stability and the Cross-Reactivity of Ochratoxin A and Citrinin
by Ingrid Bazin, Virginie Faucet-Marquis, Marie-Carmen Monje, Micheline El Khoury, Jean-Louis Marty and Annie Pfohl-Leszkowicz
Toxins 2013, 5(12), 2324-2340; https://doi.org/10.3390/toxins5122324 - 28 Nov 2013
Cited by 39 | Viewed by 8799
Abstract
Mycotoxins are secondary metabolites produced by several fungi contaminating crops. In several countries, the maximum permitted levels of mycotoxins are found in foodstuffs and feedstuffs. The common strategy of mycotoxin analysis involves extraction, clean-up and quantification by chromatography. In this paper, we analyzed [...] Read more.
Mycotoxins are secondary metabolites produced by several fungi contaminating crops. In several countries, the maximum permitted levels of mycotoxins are found in foodstuffs and feedstuffs. The common strategy of mycotoxin analysis involves extraction, clean-up and quantification by chromatography. In this paper, we analyzed the reasons of underestimation of ochratoxin A (OTA) content in wine, and overestimation of OTA in wheat, depending on the pH of the clean-up step and the simultaneous presence of citrinin (CIT). We demonstrated that the increase of pH by adding polyethylene glycol (PEG) to wine led to an underestimation of OTA by conversion of OTA into open ring ochratoxin A OP-OA. In comparing three methods of extraction and clean-up for the determination of OTA and CIT in wheat—(i) an inter-laboratory validated method for OTA in cereals using immunoaffinity column clean-up (IAC) and extraction by acetonitrile/water; (ii) a validated method using IAC and extraction with 1% bicarbonate Na; and (iii) an in-house validated method based on acid liquid/liquid extraction—we observed an overestimation of OTA after immunoaffinity clean-up when CIT is also present in the sample, whereas an underestimation was observed when OTA was alone. Under neutral and alkaline conditions, CIT was partially recognized by OTA antibodies. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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266 KiB  
Article
Comparison of Clean-Up Methods for Ochratoxin A on Wine, Beer, Roasted Coffee and Chili Commercialized in Italy
by Ambra Prelle, Davide Spadaro, Aleksandra Denca, Angelo Garibaldi and Maria Lodovica Gullino
Toxins 2013, 5(10), 1827-1844; https://doi.org/10.3390/toxins5101827 - 22 Oct 2013
Cited by 37 | Viewed by 7969
Abstract
The most common technique used to detect ochratoxin A (OTA) in food matrices is based on extraction, clean-up, and chromatography detection. Different clean-up cartridges, such as immunoaffinity columns (IAC), molecular imprinting polymers (MIP), Mycosep™ 229, Mycospin™, and Oasis® HLB (Hydrophilic Lipophilic balance) [...] Read more.
The most common technique used to detect ochratoxin A (OTA) in food matrices is based on extraction, clean-up, and chromatography detection. Different clean-up cartridges, such as immunoaffinity columns (IAC), molecular imprinting polymers (MIP), Mycosep™ 229, Mycospin™, and Oasis® HLB (Hydrophilic Lipophilic balance) as solid phase extraction were tested to optimize the purification for red wine, beer, roasted coffee and chili. Recovery, reproducibility, reproducibility, limit of detection (LOD) and limit of quantification (LOQ) were calculated for each clean-up method. IAC demonstrated to be suitable for OTA analysis in wine and beer with recovery rate >90%, as well as Mycosep™ for wine and chili. On the contrary, MIP columns were the most appropriate to clean up coffee. A total of 120 samples (30 wines, 30 beers, 30 roasted coffee, 30 chili) marketed in Italy were analyzed, by applying the developed clean-up methods. Twenty-seven out of 120 samples analyzed (22.7%: two wines, five beers, eight coffees, and 12 chili) resulted positive to OTA. A higher incidence of OTA was found in chili (40.0%) more than wine (6.6%), beers (16.6%) and coffee (26.6%). Moreover, OTA concentration in chili was the highest detected, reaching 47.8 µg/kg. Furthermore, three samples (2.5%), two wines and one chili, exceeded the European threshold. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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881 KiB  
Article
Differences in the Regulation of Ochratoxin A by the HOG Pathway in Penicillium and Aspergillus in Response to High Osmolar Environments
by Dominic Stoll, Markus Schmidt-Heydt and Rolf Geisen
Toxins 2013, 5(7), 1282-1298; https://doi.org/10.3390/toxins5071282 - 19 Jul 2013
Cited by 42 | Viewed by 6876
Abstract
Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three important ochratoxin A producing species. P. verrucosum is in addition able to produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl rich environments like salt rich dry cured [...] Read more.
Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three important ochratoxin A producing species. P. verrucosum is in addition able to produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl rich environments like salt rich dry cured foods or even salines. In this organism, the biosynthesis of ochratoxin A plays an adaptive role in this habitat. P. verrucosum generally can be found on cereals, but occasionally also on salt rich dry cured foods. In contrast A. carbonarius usually cannot be found in NaCl rich environments, but it occurs in another environment with high concentration of solutes, e.g., in sugar rich substrates like grapes and grape juices. Usually osmotic challenging conditions activate the HOG MAP kinase signal cascade, which in turn activates various osmo-regulated genes. In the current analysis, it could be demonstrated that in case of P. nordicum and P. verrucosum the NaCl induced production of ochratoxin A is correlated to the phosphorylation status of the HOG MAP kinase. Just the opposite was true for A. carbonarius. In this case, also higher amounts of NaCl in the medium lead to an increased phosphorylation status of HOG, but no increase in ochratoxin biosynthesis was observed. In contrast to the Penicillia, higher NaCl concentrations lead to a rapid cessation of growth by A. carbonarius. High glucose concentrations have much less impact on growth and the phosphorylation of HOG. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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782 KiB  
Article
Computational Design of Peptide Ligands for Ochratoxin A
by Meike Heurich, Zeynep Altintas and Ibtisam E. Tothill
Toxins 2013, 5(6), 1202-1218; https://doi.org/10.3390/toxins5061202 - 21 Jun 2013
Cited by 38 | Viewed by 8946
Abstract
In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA). A virtual library of 20 natural amino acids was used as building blocks to design a [...] Read more.
In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA). A virtual library of 20 natural amino acids was used as building blocks to design a short peptide library against ochratoxin A template using the de novo design program, LeapFrog, and the dynamic modelling software, FlexiDock. Peptide sequences were ranked according to calculated binding scores in their capacity to bind to ochratoxin A. Two high scoring peptides with the sequences N'-Cys-Ser-Ile-Val-Glu-Asp-Gly-Lys-C' (octapeptide) and N'-Gly-Pro-Ala-Gly-Ile-Asp-Gly-Pro-Ala-Gly-Ile-Arg-Cys-C' (13-mer) were selected for synthesis from the resulting database. These synthesized peptides were characterized using a microtitre plate-based binding assay and a surface plasmon resonance biosensor (Biacore 3000). The binding assay confirmed that both de novo designed peptides did bind to ochratoxin A in vitro. SPR analysis confirmed that the peptides bind to ochratoxin A, with calculated KD values of ~15.7 μM (13-mer) and ~11.8 μM (octamer). The affinity of the peptides corresponds well with the molecular modelling results, as the 13-mer peptide affinity is about 1.3-times weaker than the octapeptide; this is in accordance with the binding energy values modelled by FlexiDock. This work illustrates the potential of using computational modelling to design a peptide sequence that exhibits in vitro binding affinity for a small molecular weight toxin. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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Review

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743 KiB  
Review
A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity
by Alice Limonciel and Paul Jennings
Toxins 2014, 6(1), 371-379; https://doi.org/10.3390/toxins6010371 - 20 Jan 2014
Cited by 108 | Viewed by 10833
Abstract
Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II [...] Read more.
Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II metabolism inducibility. The effects combined would render the cell and tissue more vulnerable to oxidative stress. Indeed, Nrf2 knock out animals exhibit increased susceptibility to various types of chemical-induced injury. Several studies have shown that OTA exposure can inhibit Nrf2 responses. Such an action would initially lead to increased susceptibility to both physiological and chemical-induced cell stress. However, chronic exposure to OTA may also act as a selective pressure for somatic mutations in Nrf2 or its inhibitor Keap-1, leading to constitutive Nrf2 activation. Nrf2 overexpression confers a survival advantage and is often associated with cancer cell survival. Here we review the evidence for OTA’s role as an Nrf2 inhibitor and discuss the implications of this mechanism in nephrotoxicity and carcinogenicity. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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238 KiB  
Review
Aptamers: A Promising Tool for Ochratoxin A Detection in Food Analysis
by Amina Rhouati, Cheng Yang, Akhtar Hayat and Jean-Louis Marty
Toxins 2013, 5(11), 1988-2008; https://doi.org/10.3390/toxins5111988 - 5 Nov 2013
Cited by 113 | Viewed by 11002
Abstract
The contamination of food and feed by mycotoxins has become an increasingly serious problem. Mycotoxins represent a major risk to human and animal health, as well as economics. Herein, we focus on Ochratoxin A (OTA), which is one of the most common mycotoxins [...] Read more.
The contamination of food and feed by mycotoxins has become an increasingly serious problem. Mycotoxins represent a major risk to human and animal health, as well as economics. Herein, we focus on Ochratoxin A (OTA), which is one of the most common mycotoxins contaminating feed and foodstuffs. OTA is a secondary metabolite produced by various Aspergillus and Penicillium strains. Upon ingestion, OTA has a number of acute and chronic toxic effects. It is nephrotoxic, teratogenic, immunosuppressive, and carcinogenic (group 2B). As a consequence, some regulatory limits have been introduced on the levels of OTA in several commodities. The toxic nature of OTA demands highly sensitive and selective monitoring techniques to protect human and animal health. As alternative to traditional analytical techniques, biochemical methods for OTA analysis have attained great interest in the last few decades. They are mainly based on the integration of antibodies or aptamers as biorecognition elements in sensing platforms. However, aptamers have gained more attention in affinity-based assays because of their high affinity, specificity, stability, and their easy chemical synthesis. In this brief review, we present an overview of aptamer-based assays and their applications in OTA purification and detection, appeared in the literature in the last five years. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
304 KiB  
Review
Deleterious Effects of Mycotoxin Combinations Involving Ochratoxin A
by Maja Šegvić Klarić, Dubravka Rašić and Maja Peraica
Toxins 2013, 5(11), 1965-1987; https://doi.org/10.3390/toxins5111965 - 1 Nov 2013
Cited by 95 | Viewed by 9904
Abstract
Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than [...] Read more.
Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than one mycotoxin, earlier studies focused on the occurrence and toxicology of only OTA. Only a limited number of surveys showed that OTA co-occurs in food with mycotoxins (citrinin-CIT, penicilic acid, fumonisin B1-FB1, aflatoxins-AF) which exert nephrotoxic, carcinogenic or carcinogen-promoting activity. This review summarises the findings on OTA and its co-occurrence with the mentioned mycotoxins in food as well as experimental data on their combined toxicity. Most of the tested mycotoxin mixtures involving OTA produced additive or synergistic effects in experimental models suggesting that these combinations represent a significant health hazard. Special attention should be given to mixtures that include carcinogenic and cancer-promoting mycotoxins. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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252 KiB  
Review
Toxicity of Ochratoxin A and Its Modulation by Antioxidants: A Review
by Valeria Sorrenti, Claudia Di Giacomo, Rosaria Acquaviva, Ignazio Barbagallo, Matteo Bognanno and Fabio Galvano
Toxins 2013, 5(10), 1742-1766; https://doi.org/10.3390/toxins5101742 - 11 Oct 2013
Cited by 163 | Viewed by 11572
Abstract
Ochratoxin A (OTA) is a mycotoxin involved in the development of different types of cancers in rats, mice and humans. A growing number of in vitro and in vivo studies has been collected and has described evidence compatible with a role for oxidative [...] Read more.
Ochratoxin A (OTA) is a mycotoxin involved in the development of different types of cancers in rats, mice and humans. A growing number of in vitro and in vivo studies has been collected and has described evidence compatible with a role for oxidative stress in OTA toxicity and carcinogenicity. Because the contribution of the oxidative stress response in the development of cancers is well established, a role in OTA carcinogenicity is plausible. Several studies have been performed to try to counteract the adverse effects of oxygen radicals generated under OTA-exposure. A number of molecules with various antioxidant properties were tested, using in vivo or in vitro models. Protection against OTA-induced DNA damage, lipid peroxidation, as well as cytotoxicity were observed, further confirming the link between OTA toxicity and oxidative damage. These studies demonstrated that antioxidants are able to counteract the deleterious effects of chronic consumption or exposure to OTA and confirmed the potential effectiveness of dietary strategies to counteract OTA toxicity. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
375 KiB  
Review
Porcine/Chicken or Human Nephropathy as the Result of Joint Mycotoxins Interaction
by Stoycho D. Stoev and Stefan A. Denev
Toxins 2013, 5(9), 1503-1530; https://doi.org/10.3390/toxins5091503 - 4 Sep 2013
Cited by 20 | Viewed by 8738
Abstract
A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific [...] Read more.
A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific conditions for their growth and toxins production were briefly described. A survey was made about the most frequent nephrotoxic fungal contaminants in various feedstuffs from plant origin. In addition, their natural quantities and importance for development of mycotoxic porcine/chick nephropathy (MPN/MCN) are also explored. In addition, a survey was made of the feedstuffs representing the most favorable environment for nephrotoxic fungal growth as well as the most favorable storehouse conditions for this fungal growth were shortly described. The significance of some underestimated fungal species, which can provoke kidney damage, was studied. The importance of joint mycotoxin interaction and newly identified fungal metabolites in the complex etiology of mycotoxic nephropathy ranged in some countries is deeply investigated. The toxicity of the low contamination levels of some combinations of mycotoxins often administered by pigs and chicks in the practice was carefully studied. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
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