Toxicological Effects of Mycotoxins

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

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 16055

Special Issue Editor


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Guest Editor
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
Interests: gut health; fusarium mycotoxins; interaction with bacterial enteric diseases
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Special Issue Information

Dear Colleagues,

The assessment of the risk for a given mycotoxin is based on risk characterization, combining three major pillars: hazard identification, hazard characterization, and exposure assessment. In this Special Issue we would like to focus on the first two pillars, aiming to identify and characterize the risk of a given mycotoxin by assessing both its toxicokinetics and its toxicity or toxicodynamics. Toxicokinetics include the so-called ADME processes (i.e., absorption, distribution, metabolism, and excretion), and determines the rate and extent at which the disposition of a toxin takes place. The toxicokinetic properties of a given toxin reflect its absolute internal dose, and comprise processes such as gastric and intestinal stability, rate and extent of oral absorption, presystemic elimination (first pass, metabolism in gut and/or liver), systemic elimination (metabolism and excretion) determining the total body clearance, and specific biological barriers determining the volume of distribution. Each of these processes may show species-specific differences. Next, toxicodynamics describe the toxicological characteristics (among others, cytotoxicity, genotoxicity (mutagenicity and carcinogenicity), mode of action, and dose–response relationship) of mycotoxins. Besides mycotoxin risk assessment, a toxicokinetic and toxicodynamic approach can also be applied to define the efficacy, mode of action, and safety of mycotoxin mitigation strategies.

This Special Issue aims to gather innovative research on toxicokinetics, toxicity, or toxicodynamics, and the integration of toxicokinetic and toxicodynamic processes of mycotoxins in animals and humans, such as papers describing the toxicokinetic properties of emerging mycotoxins, mycotoxin metabolites, or comparative inter-species approaches, as well as new approaches and alternatives for toxicity testing and toxicokinetic/toxicodynamic approaches to evaluating postharvest mycotoxin mitigation strategies.

Prof. Dr. Gunther Antonissen
Guest Editor

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Keywords

  • Mode of action
  • Mycotoxin
  • Toxicity
  • Toxicodynamics
  • Toxicokinetics

Published Papers (5 papers)

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Research

13 pages, 4474 KiB  
Article
Zearalenone Exposure Disrupts Blood–Testis Barrier Integrity through Excessive Ca2+-Mediated Autophagy
by Jinjin She, Nannan Feng, Wanglong Zheng, Hao Zheng, Peirong Cai, Hui Zou, Yan Yuan, Jianhong Gu, Zongping Liu and Jianchun Bian
Toxins 2021, 13(12), 875; https://doi.org/10.3390/toxins13120875 - 8 Dec 2021
Cited by 21 | Viewed by 2892
Abstract
Zearalenone (ZEA), a common mycotoxin in grains and animal feeds, has been associated with male reproductive disorders. However, the potential toxicity mechanism of ZEA is not fully understood. In this study, in vivo and in vitro models were used to explore the effects [...] Read more.
Zearalenone (ZEA), a common mycotoxin in grains and animal feeds, has been associated with male reproductive disorders. However, the potential toxicity mechanism of ZEA is not fully understood. In this study, in vivo and in vitro models were used to explore the effects of ZEA on the blood–testis barrier (BTB) and related molecular mechanisms. First, male BALB/C mice were administered ZEA orally (40 mg/kg·bw) for 5–7 d. Sperm motility, testicular morphology, and expressions of BTB junction proteins and autophagy-related proteins were evaluated. In addition, TM4 cells (mouse Sertoli cells line) were used to delineate the molecular mechanisms that mediate the effects of ZEA on BTB. Our results demonstrated that ZEA exposure induced severe testicular damage in histomorphology and an ultrastructural, time-dependent decrease in the expression of blood–testis barrier junction-related proteins, accompanied by an increase in the expression of autophagy-related proteins. Additionally, similar to the in vitro results, the dose-dependent treatment of ZEA increased the level of cytoplasmic Ca2+ and the levels of the autophagy markers LC3-II and p62, in conjunction with a decrease in the BTB junction proteins occludin, claudin-11, and Cx43, with the dislocation of the gap junction protein Cx43. Meanwhile, inhibition of autophagy by CQ and 3-MA or inhibition of cytoplasmic Ca2+ by BAPTA-AM was sufficient to reduce the effects of ZEA on the TM4 cell BTB. To summarize, this study emphasizes the role of Ca2+-mediated autophagy in ZEA-induced BTB destruction, which deepens our understanding of the molecular mechanism of ZEA-induced male reproductive disorders. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxins)
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17 pages, 1923 KiB  
Article
Grape Seed Proanthocyanidin Ameliorates FB1-Induced Meiotic Defects in Porcine Oocytes
by Wenhui Li, Yijing He, Hongyu Zhao, Lei Peng, Jia Li, Rong Rui and Shiqiang Ju
Toxins 2021, 13(12), 841; https://doi.org/10.3390/toxins13120841 - 25 Nov 2021
Cited by 6 | Viewed by 2234
Abstract
Fumonisin B1 (FB1), as the most prevalent and toxic fumonisin, poses a health threat to humans and animals. The cytotoxicity of FB1 is closely related to oxidative stress and apoptosis. The purpose of this study is to explore whether [...] Read more.
Fumonisin B1 (FB1), as the most prevalent and toxic fumonisin, poses a health threat to humans and animals. The cytotoxicity of FB1 is closely related to oxidative stress and apoptosis. The purpose of this study is to explore whether Grape seed proanthocyanidin (GSP), a natural antioxidant, could alleviate the meiotic maturation defects of oocytes caused by FB1 exposure. Porcine cumulus oocyte complexes (COCs) were treated with 30 μM FB1 alone or cotreated with 100, 200 and 300 μM GSP during in vitro maturation for 44 h. The results show that 200 μM GSP cotreatment observably ameliorated the toxic effects of FB1 exposure, showing to be promoting first polar body extrusion and improving the subsequent cleavage rate and blastocyst development rate. Moreover, 200 μM GSP cotreatment restored cell cycle progression, reduced the proportion of aberrant spindles, improved actin distribution and protected mitochondrial function in FB1-exposed oocytes. Furthermore, reactive oxygen species (ROS) generation was significantly decreased and the mRNA levels of CAT, SOD2 and GSH-PX were obviously increased in the 200 μM GSP cotreatment group. Notably, the incidence of early apoptosis and autophagy level were also significantly decreased after GSP cotreatment and the mRNA expression levels of BAX, CASPASE3, LC3 and ATG5 were markedly decreased, whereas BCL2 and mTOR were observably increased in the oocytes after GSP cotreatment. Together, these results indicate that GSP could exert significant preventive effects on FB1-induced oocyte defects by ameliorating oxidative stress through repairing mitochondrial dysfunction. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxins)
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19 pages, 1140 KiB  
Article
Effects of Deoxynivalenol and Fumonisins on Broiler Gut Cytoprotective Capacity
by Vasileios Paraskeuas, Eirini Griela, Dimitrios Bouziotis, Konstantinos Fegeros, Gunther Antonissen and Konstantinos C. Mountzouris
Toxins 2021, 13(10), 729; https://doi.org/10.3390/toxins13100729 - 16 Oct 2021
Cited by 12 | Viewed by 2967
Abstract
Mycotoxins are a crucial problem for poultry production worldwide. Two of the most frequently found mycotoxins in feedstuffs are deoxynivalenol (DON) and fumonisins (FUM) which adversely affect gut health and poultry performance. The current knowledge on DON and FUM effects on broiler responses [...] Read more.
Mycotoxins are a crucial problem for poultry production worldwide. Two of the most frequently found mycotoxins in feedstuffs are deoxynivalenol (DON) and fumonisins (FUM) which adversely affect gut health and poultry performance. The current knowledge on DON and FUM effects on broiler responses relevant for gut detoxification, antioxidant capacity, and health is still unclear. The aim of this study was to assess a range of selected molecular intestinal biomarkers for their responsiveness to the maximum allowable European Union dietary levels for DON (5 mg/kg) and FUM (20 mg/kg) in broilers. For the experimental purpose, a challenge diet was formulated, and biomarkers relevant for detoxification, antioxidant response, stress, inflammation, and integrity were profiled across the broiler intestine. The results reveal that DON significantly (p < 0.05) induced aryl hydrocarbon receptor (AhR) and cytochrome P450 enzyme (CYP) expression mainly at the duodenum. Moreover, DON and FUM had specific significant (p < 0.05) effects on the antioxidant response, stress, inflammation, and integrity depending on the intestinal segment. Consequently, broiler molecular responses to DON and FUM assessed via a powerful palette of biomarkers were shown to be mycotoxin and intestinal site specific. The study findings could be highly relevant for assessing various dietary bioactive components for protection against mycotoxins. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxins)
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14 pages, 3124 KiB  
Article
In Vitro and In Vivo Analysis of Ochratoxin A-Derived Glucuronides and Mercapturic Acids as Biomarkers of Exposure
by Raphael Dekant, Michael Langer, Maria Lupp, Cynthia Adaku Chilaka and Angela Mally
Toxins 2021, 13(8), 587; https://doi.org/10.3390/toxins13080587 - 23 Aug 2021
Cited by 5 | Viewed by 3069
Abstract
Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with [...] Read more.
Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with considerable uncertainty. While biomarker-based approaches may contribute to improved exposure assessment, there is yet insufficient data on urinary metabolites of OTA and their relation to external dose to allow reliable estimates of daily intake. This study was designed to assess potential species differences in phase II biotransformation in vitro and to establish a correlation between urinary OTA-derived glucuronides and mercapturic acids and external exposure in rats in vivo. In vitro analyses of OTA metabolism using the liver S9 of rats, humans, rabbits and minipigs confirmed formation of an OTA glucuronide but provided no evidence for the formation of OTA-derived mercapturic acids to support their use as biomarkers. Similarly, OTA-derived mercapturic acids were not detected in urine of rats repeatedly dosed with OTA, while indirect analysis using enzymatic hydrolysis of the urine samples prior to LC–MS/MS established a linear relationship between urinary glucuronide excretion and OTA exposure. These results support OTA-derived glucuronides but not mercapturic acids as metabolites suitable for biomonitoring. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxins)
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15 pages, 699 KiB  
Article
Calcination Improves the In Vivo Efficacy of a Montmorillonite Clay to Bind Aflatoxin G1 in Broiler Chickens: A Toxicokinetic Approach
by Roua Rejeb, Siegrid De Baere, Mathias Devreese, Richard Ducatelle, Siska Croubels, Madiha Hadj Ayed, Achraf Ghorbal and Gunther Antonissen
Toxins 2020, 12(10), 660; https://doi.org/10.3390/toxins12100660 - 18 Oct 2020
Cited by 1 | Viewed by 2851
Abstract
The goal of this study was to investigate the toxicokinetic characteristics of aflatoxin G1 (AFG1) in broiler chickens and the effect of calcination of a Tunisian montmorillonite clay on the in vivo absorption of AFG1. In this study, broiler chickens were randomly distributed [...] Read more.
The goal of this study was to investigate the toxicokinetic characteristics of aflatoxin G1 (AFG1) in broiler chickens and the effect of calcination of a Tunisian montmorillonite clay on the in vivo absorption of AFG1. In this study, broiler chickens were randomly distributed into four groups of 10 animals. Group 1 was administered AFG1 (2 mg/kg body weight (BW)) by single intravenous injection (IV), group 2 received an intra-crop bolus (PO) of AFG1 without any clay, group 3 was dosed AFG1 PO together with an oral bolus of purified clay (CP), and group 4 received AFG1 PO with an oral bolus of calcined clay. A significant difference in the area under the curve (AUC0-t) was observed for group 4 (6.78 ± 4.24 h*ng/mL) in comparison with group 2 (12.83 ± 4.19 h*ng/mL). A significant reduction of the oral bioavailability of AFG1 was observed for group 4 (7.61 ± 4.76%) compared with group 2 (14.40 ± 4.70%), while no significant effect was observed of CP. In this experiment, no phase I nor phase II metabolites of AFG1 were observed. These findings confirm that calcination of the purified montmorillonite clay enhances the adsorption of AFG1 in the gastrointestinal tract after oral administration, thereby reducing its bioavailability, thus reducing its toxic effects. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxins)
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