Metabolism of Mycotoxins by Animals and Microbes

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 11604

Special Issue Editor


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Guest Editor
University of Natural Resources and Life Sciences, Vienna, Department IFA-Tulln, Institute of Bioanalytics and Agro-Metabolomics

Special Issue Information

Dear Colleagues,

The more we know about the metabolism and biochemistry of mycotoxins, the better the exposure to mycotoxins can be assessed and the better the negative effects caused by mycotoxins can be mitigated. Studying the metabolism of mycotoxins can lead to the discovery of novel biomarkers for estimating mycotoxin exposure. Likewise, knowledge of metabolization is crucial in the toxicity assessment of mycotoxins in different animal species. Furthermore, investigating the metabolization of mycotoxins by microbes is a vital part in the discovery and development of mycotoxin inactivators.

While the in vivo fate of selected mycotoxins has been extensively studied, the metabolism of other mycotoxins has at best only partly been elucidated. In addition, for some of the well-investigated mycotoxins, great differences in metabolism have been discovered between animal species. For instance, when only glucuronidation was considered as a metabolization pathway of deoxynivalenol (DON) in animals, biological recoveries of DON were below 20% in species such as cows, rats and chickens. The microbial transformation by de-epoxidation and, as only recently demonstrated, the pathways of sulfation and sulfonation provided the missing link. Considering that it took decades to elucidate the in vivo fate of one of the most common and most studied mycotoxins, more timely research on the metabolism of other mycotoxins is warranted.

This Special Issue of Toxins on ‘Metabolism of Mycotoxins by Animals and Microbes’ aims to provide a comprehensive overview of all topics related to the metabolism of mycotoxins. These include, among others, animal experiments on the metabolism of masked or emerging mycotoxins, ADME studies of mycotoxins in different animal species, toxicological studies in vivo and in vitro, the analytical methodologies involved, detoxification strategies based on microbial action, in vivo testing of feed additives, and biomarker research.

Dr. Heidi E. Schwartz-Zimmermann
Guest Editor

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Keywords

  • Mycotoxin biomarkers
  • Metabolization
  • Animals
  • Humans
  • Analytical methods
  • Toxicokinetics
  • Detoxification
  • In vivo
  • In vitro

Published Papers (4 papers)

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Research

17 pages, 4267 KiB  
Article
Biomarkers of Deoxynivalenol, Citrinin, Ochratoxin A and Zearalenone in Pigs after Exposure to Naturally Contaminated Feed Close to Guidance Values
by Agnieszka Tkaczyk, Piotr Jedziniak, Łukasz Zielonka, Michał Dąbrowski, Piotr Ochodzki and Adrianna Rudawska
Toxins 2021, 13(11), 750; https://doi.org/10.3390/toxins13110750 - 22 Oct 2021
Cited by 9 | Viewed by 2597
Abstract
This study applied multi-mycotoxin liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methods to determine the biomarkers of exposure in urine and serum samples from a dose-response study with pigs. The 24 studied pigs were divided into three groups: a control and two [...] Read more.
This study applied multi-mycotoxin liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methods to determine the biomarkers of exposure in urine and serum samples from a dose-response study with pigs. The 24 studied pigs were divided into three groups: a control and two experimental ones (with different levels of feed contamination). They were exposed to feed prepared from cereals contaminated with deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA) and citrinin (CIT) for 14 days. After that, both experimental groups received the same feed as the control group for the next 14 days to determine the kinetics of the disappearance of mycotoxin biomarkers. Urine samples were collected daily in the morning and blood samples—eight-times during the experiment. The study reported herein was the first prolonged exposure experiment for multiple mycotoxins like OTA and CIT in pigs. The urinary and serum levels of all biomarkers correlated well with the respective toxin intake; thereby demonstrating that they are suitable biomarkers of exposure in pigs. Urine is a good candidate to monitor DON, ZEN, OTA, CIT exposure while serum may be used to monitor DON, OTA and CIT. Additionally, OTA has even been quantified in both matrices in the experimental groups two weeks after changing the contaminated feed back to the control, this result differed from those produced by the other mycotoxins which were only quantified during the first two weeks. Therefore both matrices are suitable candidates to monitor prolonged OTA exposure in pigs. Full article
(This article belongs to the Special Issue Metabolism of Mycotoxins by Animals and Microbes)
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14 pages, 1823 KiB  
Article
Controlled Production of Zearalenone-Glucopyranoside Standards with Cunninghamella Strains Using Sulphate-Depleted Media
by Jeroen Peters, Edward Ash, Arjen Gerssen, Ruud Van Dam, Maurice C. R. Franssen and Michel W. F. Nielen
Toxins 2021, 13(6), 366; https://doi.org/10.3390/toxins13060366 - 21 May 2021
Cited by 2 | Viewed by 2109
Abstract
In recent years, conjugated mycotoxins have gained increasing interest in food safety, as their hydrolysis in human and animal intestines leads to an increase in toxicity. For the production of zearalenone (ZEN) glycosides reference standards, we applied Cunninghamellaelegans and Cunninghamella echinulata fungal [...] Read more.
In recent years, conjugated mycotoxins have gained increasing interest in food safety, as their hydrolysis in human and animal intestines leads to an increase in toxicity. For the production of zearalenone (ZEN) glycosides reference standards, we applied Cunninghamellaelegans and Cunninghamella echinulata fungal strains. A sulphate-depleted medium was designed for the preferred production of ZEN glycosides. Both Cunninghamella strains were able to produce zearalenone-14-β-D-glucopyranoside (Z14G), zearalenone-16-β-D-glucopyranoside (Z16G) and zearalenone-14-sulphate (Z14S). In a rich medium, Cunninghamellaelegans preferably produced Z14S, while Cunninghamellaechinulata preferably produced Z14G. In the sulphate-depleted medium a dramatic change was observed for Cunninghamellaelegans, showing preferred production of Z14G and Z16G. From 2 mg of ZEN in sulphate-depleted medium, 1.94 mg of Z14G and 0.45 mg of Z16G were produced. Following preparative Liquid Chromatography-Mass Spectrometry (LC-MS) purification, both fractions were submitted to 1H and 13C NMR and High-Resolution Mass Spectrometry (HRMS). These analyses confirmed that the purified fractions were indeed Z14G and Z16G. In conclusion, the presented research shows that a single Cunninghamella strain can be an effective and efficient tool for the controlled biotransformation of ZEN glycosides and other ZEN metabolites. Additionally, the biotransformation method was extended to zearalanone, β-zearalenol and other mycotoxins. Full article
(This article belongs to the Special Issue Metabolism of Mycotoxins by Animals and Microbes)
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18 pages, 2430 KiB  
Article
Metabolism of Zearalenone in the Rumen of Dairy Cows with and without Application of a Zearalenone-Degrading Enzyme
by Christiane Gruber-Dorninger, Johannes Faas, Barbara Doupovec, Markus Aleschko, Christian Stoiber, Andreas Höbartner-Gußl, Karin Schöndorfer, Manuela Killinger, Qendrim Zebeli and Dian Schatzmayr
Toxins 2021, 13(2), 84; https://doi.org/10.3390/toxins13020084 - 22 Jan 2021
Cited by 19 | Viewed by 3272
Abstract
The mycotoxin zearalenone (ZEN) is a frequent contaminant of animal feed and is well known for its estrogenic effects in animals. Cattle are considered less sensitive to ZEN than pigs. However, ZEN has previously been shown to be converted to the highly estrogenic [...] Read more.
The mycotoxin zearalenone (ZEN) is a frequent contaminant of animal feed and is well known for its estrogenic effects in animals. Cattle are considered less sensitive to ZEN than pigs. However, ZEN has previously been shown to be converted to the highly estrogenic metabolite α-zearalenol (α-ZEL) in rumen fluid in vitro. Here, we investigate the metabolism of ZEN in the reticulorumen of dairy cows. To this end, rumen-fistulated non-lactating Holstein Friesian cows (n = 4) received a one-time oral dose of ZEN (5 mg ZEN in 500 g concentrate feed) and the concentrations of ZEN and ZEN metabolites were measured in free rumen liquid from three reticulorumen locations (reticulum, ventral sac and dorsal mat layer) during a 34-h period. In all three locations, α-ZEL was the predominant ZEN metabolite and β-zearalenol (β-ZEL) was detected in lower concentrations. ZEN, α-ZEL and β-ZEL were eliminated from the ventral sac and reticulum within 34 h, yet low concentrations of ZEN and α-ZEL were still detected in the dorsal mat 34 h after ZEN administration. In a second step, we investigated the efficacy of the enzyme zearalenone hydrolase ZenA (EC 3.1.1.-, commercial name ZENzyme®, BIOMIN Holding GmbH, Getzersdorf, Austria) to degrade ZEN to the non-estrogenic metabolite hydrolyzed zearalenone (HZEN) in the reticulorumen in vitro and in vivo. ZenA showed a high ZEN-degrading activity in rumen fluid in vitro. When ZenA was added to ZEN-contaminated concentrate fed to rumen-fistulated cows (n = 4), concentrations of ZEN, α-ZEL and β-ZEL were significantly reduced in all three reticulorumen compartments compared to administration of ZEN-contaminated concentrate without ZenA. Upon ZenA administration, degradation products HZEN and decarboxylated HZEN were detected in the reticulorumen. In conclusion, endogenous metabolization of ZEN in the reticulorumen increases its estrogenic potency due to the formation of α-ZEL. Our results suggest that application of zearalenone hydrolase ZenA as a feed additive may be a promising strategy to counteract estrogenic effects of ZEN in cattle. Full article
(This article belongs to the Special Issue Metabolism of Mycotoxins by Animals and Microbes)
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13 pages, 969 KiB  
Article
Toxicokinetics of Hydrolyzed Fumonisin B1 after Single Oral or Intravenous Bolus to Broiler Chickens Fed a Control or a Fumonisins-Contaminated Diet
by Gunther Antonissen, Siegrid De Baere, Barbara Novak, Dian Schatzmayr, Danica den Hollander, Mathias Devreese and Siska Croubels
Toxins 2020, 12(6), 413; https://doi.org/10.3390/toxins12060413 - 21 Jun 2020
Cited by 9 | Viewed by 2603
Abstract
The toxicokinetics (TK) of hydrolyzed fumonisin B1 (HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B1, 3.3 mg B2 and 1.5 mg B3/kg [...] Read more.
The toxicokinetics (TK) of hydrolyzed fumonisin B1 (HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B1, 3.3 mg B2 and 1.5 mg B3/kg feed) for two weeks, followed by a single oral (PO) or intravenous (IV) dose of 1.25 mg/kg bodyweight (BW) of HFB1. Fumonisin B1 (FB1), its partially hydrolyzed metabolites pHFB1a and pHFB1b, and fully hydrolyzed metabolite HFB1, were determined in chicken plasma using a validated ultra-performance liquid chromatography–tandem mass spectrometry method. None of the broiler chicken showed clinical symptoms of fumonisins (FBs) or HFB1 toxicity during the trial, nor was an aberration in body weight observed between the animals fed the FBs-contaminated diet and those fed the control diet. HFB1 was shown to follow a two-compartmental pharmacokinetic model with first order elimination in broiler chickens after IV administration. Toxicokinetic parameters of HFB1 demonstrated a total body clearance of 16.39 L/kg·h and an intercompartmental flow of 8.34 L/kg·h. Low levels of FB1 and traces of pHFB1b were found in plasma of chickens fed the FBs-contaminated diet. Due to plasma concentrations being under the limit of quantification (LOQ) after oral administration of HFB1, no toxicokinetic modelling could be performed in broiler chickens after oral administration of HFB1. Moreover, no phase II metabolites, nor N-acyl-metabolites of HFB1 could be detected in this study. Full article
(This article belongs to the Special Issue Metabolism of Mycotoxins by Animals and Microbes)
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