Toxic Effect of Mycotoxins

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

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 42143

Special Issue Editor

Toxalim (Research Centre in Food Toxicology), University of Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France
Interests: mycotoxins; proteomics; integrative biology; intestinal pathophysiology; animal sciences

Special Issue Information

Dear Colleagues,

Understanding the individual toxicity of regulated and emerging toxins is essential to establishing their associated risk and contribution to disease pathogenesis. In this sense, the use and integration of global technical approaches, such as -omics approaches, is particularly useful for investigating the adverse outcome pathways and toxicity of mycotoxins with very little a priori information, as well as identifying specific toxic endpoints of “biomarkers of effect”. The latter is especially useful when investigating the toxic interaction of mycotoxins. Indeed, the simultaneous presence of different mycotoxins is potentially able to produce synergistic toxic effects that cannot be predicted from the toxicity of individual mycotoxins. Interaction studies using known and/or new toxicity endpoints are largely needed for multiexposure risk assessment.

Recent studies have associated the toxicity of regulated mycotoxins and the development and/or aggravation of known diseases, particularly when associated with other factors such as stress or obesity as well as other pathogens or toxicants. Likewise, it is becoming evident that several mycotoxins have insidious toxic effects under sub-acute and chronic exposure conditions. However, the exact mechanisms leading to such effects are poorly understood.

Recent advances in the characterization of the metabolome of mycotoxigenic fungal species are providing lists of newly discovered molecules. It is important to associate these discoveries with the development and validation of high-throughput toxicity screening assays to identify new emerging mycotoxins.

We look forward to receiving your contributions for this Special Issue in the form of original research or review papers aiming at advancing the knowledge of the toxicity of any mycotoxin(s) in any species, alone or in combination. Original research articles or reviews on toxicity screening methodology development, including biomarkers of effect, are also welcome.

Dr. Laura Soler-Vasco
Guest Editor

Manuscript Submission Information

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Keywords

  • mycotoxins
  • risk assessment
  • mycotoxin interaction
  • proteomics
  • transcriptomics
  • metabolomics
  • biomarker of effect
  • toxicity screening

Published Papers (10 papers)

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Research

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14 pages, 2401 KiB  
Article
Tissular Genomic Responses to Oral FB1 Exposure in Pigs
by Léonie Dopavogui, Arnaud Polizzi, Anne Fougerat, Pascal Gourbeyre, Chloé Terciolo, Wendy Klement, Philippe Pinton, Joëlle Laffite, Anne-Marie Cossalter, Jean-Denis Bailly, Olivier Puel, Yannick Lippi, Claire Naylies, Hervé Guillou, Isabelle P. Oswald and Nicolas Loiseau
Toxins 2022, 14(2), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14020083 - 22 Jan 2022
Cited by 2 | Viewed by 2263
Abstract
Fumonisin B1 (FB1) is a widespread mycotoxin produced by fungal Fusarium species—mainly in maize, one of the plants most commonly used for food and feed. Pigs and horses are the animal species most susceptible to this mycotoxin. FB1 exposure can cause highly diverse [...] Read more.
Fumonisin B1 (FB1) is a widespread mycotoxin produced by fungal Fusarium species—mainly in maize, one of the plants most commonly used for food and feed. Pigs and horses are the animal species most susceptible to this mycotoxin. FB1 exposure can cause highly diverse clinical symptoms, including hepatotoxicity, immunotoxicity, and intestinal barrier function disturbance. Inhibition of ceramide synthetase is a well-understood ubiquitous molecular mechanism of FB1 toxicity, but other more tissue-specific effects remain to be elucidated. To investigate the effects of FB1 in different exposed tissues, we cross-analyzed the transcriptomes of fours organs: liver, jejunum, jejunal Peyer’s patches, and spleen. During a four-week study period, pigs were fed a control diet or a FB1-contaminated diet (10 mg/kg feed). In response to oral FB1 exposure, we observed common biological processes in the four organs, including predominant and recurrent processes (extracellular matrix organization, integrin activation, granulocyte chemotaxis, neutrophil migration, and lipid and sterol homeostasis), as well as more tissue-specific processes that appeared to be related to lipid outcomes (cell cycle regulation in jejunum, and gluconeogenesis in liver). Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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17 pages, 1259 KiB  
Article
Ecotoxicological Effects of Aflatoxins on Earthworms under Different Temperature and Moisture Conditions
by Tanya Fouché, Sarina Claassens and Mark Steve Maboeta
Toxins 2022, 14(2), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14020075 - 21 Jan 2022
Cited by 3 | Viewed by 2886
Abstract
Aflatoxin contamination remains one of the most important threats to food safety and human health. Aflatoxins are mainly found in soil, decaying plant material and food storage systems and are particularly abundant during drought stress. Regulations suggest the disposal of aflatoxin-contaminated crops by [...] Read more.
Aflatoxin contamination remains one of the most important threats to food safety and human health. Aflatoxins are mainly found in soil, decaying plant material and food storage systems and are particularly abundant during drought stress. Regulations suggest the disposal of aflatoxin-contaminated crops by incorporation into the soil for natural degradation. However, the fate and consequences of aflatoxin in soil and on soil organisms providing essential ecological services remain unclear and could potentially pose a risk to soil health and productivity. The protection of soil biodiversity and ecosystem services are essential for the success of the declared United Nations Decade on Ecosystem Restoration. The focus of this study was to investigate the toxicological consequences of aflatoxins to earthworms’ survival, growth, reproduction and genotoxicity under different temperature and moisture conditions. Results indicated an insignificant effect of aflatoxin concentrations between 10 and 100 µg/kg on the survival, growth and reproduction but indicated a concentration-dependent increase in DNA damage at standard testing conditions. However, the interaction of the toxin with different environmental conditions, particularly low moisture, resulted in significantly reduced reproduction rates and increased DNA damage in earthworms. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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15 pages, 3558 KiB  
Article
The Efficacy of a Smectite-Based Mycotoxin Binder in Reducing Aflatoxin B1 Toxicity on Performance, Health and Histopathology of Broiler Chickens
by Ismail Zabiulla, Venkataramaiah Malathi, H. V. L. N. Swamy, Jaya Naik, Lane Pineda and Yanming Han
Toxins 2021, 13(12), 856; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13120856 - 01 Dec 2021
Cited by 14 | Viewed by 3818
Abstract
The aim of the experiment was to investigate the efficacy of a smectite-based clay binder (Toxo-MX) in reducing the toxicological effects of aflatoxin B1 (AFB1) in commercial broiler chickens. A total of 450 one-day old male broiler chickens were randomly [...] Read more.
The aim of the experiment was to investigate the efficacy of a smectite-based clay binder (Toxo-MX) in reducing the toxicological effects of aflatoxin B1 (AFB1) in commercial broiler chickens. A total of 450 one-day old male broiler chickens were randomly allocated into three treatment groups with ten replicates of 15 birds each in a 42-day feeding experiment. The dietary treatments included a negative control (NC, a basal diet with no AFB1 and binder), a positive control (PC, a basal diet contaminated with 500 ppb of AFB1) and a smectite-based mycotoxin binder(Toxo-MX, PC with smectite clay binder). AFB1 challenge resulted in 14 to 24% depression in growth performance, elevated levels of aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT), organ enlargement and immuno-suppression.As compared to PC, feeding of Toxo-MX improved the final weight (15%; p < 0.0001), average daily gain (ADG) (15%; p < 0.001) and feed efficiency of broilers (13%; p < 0.0003) but did not have any effects on liver enzyme activities. Supplementation of smectite claysignificantly increased serum globulin levels and reduced the weight of the liver (p < 0.05) as compared to AFB1-fed broiler chickens. The severity of lesions (inflammatory and degenerative changes) observed in the liver, kidney, heart, pancreas, and lymphoid organs in PC birds was reduced by feeding smectite clay. The immuno-suppression caused by AFB1 was moderately ameliorated in Toxo-MX groupby stimulating the production of antibodies against IBD at day 42 (p < 0.05). In conclusion, dietary supplementation of a smectite-based mycotoxin binder to the diet containing AFB1 improved growth performance, reduced toxicological effects in liver and improved humoral immune response in broilers, suggesting its protective effect against aflatoxicosis. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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16 pages, 1245 KiB  
Article
Exposure to Zearalenone Leads to Metabolic Disruption and Changes in Circulating Adipokines Concentrations in Pigs
by Veronika Nagl, Bertrand Grenier, Philippe Pinton, Ursula Ruczizka, Maximiliane Dippel, Moritz Bünger, Isabelle P. Oswald and Laura Soler
Toxins 2021, 13(11), 790; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13110790 - 08 Nov 2021
Cited by 9 | Viewed by 2179
Abstract
Zearalenone (ZEN) is a mycotoxin classified as an endocrine disruptor. Many endocrine disruptors are also metabolic disruptors able to modulate energy balance and inflammatory processes in a process often involving a family of protein hormones known as adipokines. The aim of our study [...] Read more.
Zearalenone (ZEN) is a mycotoxin classified as an endocrine disruptor. Many endocrine disruptors are also metabolic disruptors able to modulate energy balance and inflammatory processes in a process often involving a family of protein hormones known as adipokines. The aim of our study was to elucidate the role of ZEN as metabolic disruptor in pigs by investigating the changes in energy balance and adipokines levels in response to different treatment diets. To this end, weaned piglets (n = 10/group) were exposed to either basal feed or feed contaminated with 680 and 1620 µg/kg ZEN for 28 days. Serum samples collected at days 7 and 21 were subjected to biochemistry analysis, followed by determination of adipokine levels using a combined approach of protein array and ELISA. Results indicate that ZEN has an impact on lipid and glucose metabolism that was different depending on the dose and time of exposure. In agreement with these changes, ZEN altered circulating adipokines concentrations, inducing significant changes in adiponectin, resistin, and fetuin B. Our results suggest that ZEN may function as a natural metabolism-disrupting chemical. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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16 pages, 4361 KiB  
Article
Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
by Hikaru Hanyu, Yuki Yokoi, Kiminori Nakamura, Tokiyoshi Ayabe, Keisuke Tanaka, Kinuko Uno, Katsuhiro Miyajima, Yuki Saito, Ken Iwatsuki, Makoto Shimizu, Miki Tadaishi and Kazuo Kobayashi-Hattori
Toxins 2020, 12(10), 610; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100610 - 24 Sep 2020
Cited by 16 | Viewed by 3023
Abstract
The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a [...] Read more.
The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a culture medium (basolateral exposure) using three-dimensional mouse intestinal organoids (enteroids). The influx test using fluorescein-labeled dextran showed that basolateral DON exposure (1 micromolar (µM) disrupted intestinal barrier functions in enteroids compared with luminal DON exposure at the same concentration. Moreover, an immunofluorescence experiment of intestinal epithelial proteins, such as E-cadherin, claudin, zonula occludens-1 (ZO-1), and occludin, exhibited that only basolateral DON exposure broke down intestinal epithelial integrity. A time-lapse analysis using enteroids from leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-enhanced green fluorescence protein (EGFP) transgenic mice and 5-ethynyl-2-deoxyuridine (EdU) assay indicated that only the basolateral DON exposure, but not luminal DON exposure, suppressed Lgr5+ stem cell count and proliferative cell ratio, respectively. These results revealed that basolateral DON exposure has larger impacts on intestinal barrier function and stem cells than luminal DON exposure. This is the first report that DON had different impacts on intestinal stem cells depending on the administration route. In addition, RNA sequencing analysis showed different expression of genes among enteroids after basolateral and luminal DON exposure. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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19 pages, 376 KiB  
Article
Individual and Combined In Vitro Effects of Deoxynivalenol and Zearalenone on Boar Semen
by Panagiotis D. Tassis, Ioannis A. Tsakmakidis, Veronika Nagl, Nicole Reisinger, Eleni Tzika, Christiane Gruber-Dorninger, Ilias Michos, Nikolaos Mittas, Athina Basioura and Dian Schatzmayr
Toxins 2020, 12(8), 495; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12080495 - 01 Aug 2020
Cited by 14 | Viewed by 3079
Abstract
Mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) can negatively affect pig health. However, little is known about their effects on boar semen. We assessed the individual and combined effects of DON and ZEN on boar semen in vitro. In a pretrial, we determined the [...] Read more.
Mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) can negatively affect pig health. However, little is known about their effects on boar semen. We assessed the individual and combined effects of DON and ZEN on boar semen in vitro. In a pretrial, we determined the minimum dose (MiD) of each mycotoxin that induces a significant alteration of sperm progressive motility, as investigated using computer-assisted semen analysis (CASA). In the main trial, the individual and combined effects of each mycotoxin’s MiD on sperm motility and kinetics (CASA analysis), morphology (SpermBlue staining), viability (calcein-propidium iodide staining), membrane functional status (hypoosmotic swelling test), and chromatin integrity (acridine orange staining) were analyzed. Pretrial results suggested a MiD of 50.6 μM and 62.8 μM for DON and ZEN, respectively. In the main trial, DON and ZEN administered at MiD significantly affected CASA parameters (e.g., increase of immotile spermatozoa, reduction of progressive motile spermatozoa), decreased sperm viability, and affected sperm morphology (head abnormalities) and membrane functional status. DON and ZEN showed less than additive effects on most parameters tested and a synergistic effect on viability and on two CASA parameters. In conclusion, DON and ZEN showed individual and combined toxic effects on boar semen in vitro. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)

Review

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25 pages, 1245 KiB  
Review
Citrinin Mycotoxin Contamination in Food and Feed: Impact on Agriculture, Human Health, and Detection and Management Strategies
by Madhu Kamle, Dipendra Kumar Mahato, Akansha Gupta, Shikha Pandhi, Nitya Sharma, Bharti Sharma, Sadhna Mishra, Shalini Arora, Raman Selvakumar, Vivek Saurabh, Jyoti Dhakane-Lad, Manoj Kumar, Sreejani Barua, Arvind Kumar, Shirani Gamlath and Pradeep Kumar
Toxins 2022, 14(2), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14020085 - 23 Jan 2022
Cited by 37 | Viewed by 7954
Abstract
Citrinin (CIT) is a mycotoxin produced by different species of Aspergillus, Penicillium, and Monascus. CIT can contaminate a wide range of foods and feeds at any time during the pre-harvest, harvest, and post-harvest stages. CIT can be usually found in [...] Read more.
Citrinin (CIT) is a mycotoxin produced by different species of Aspergillus, Penicillium, and Monascus. CIT can contaminate a wide range of foods and feeds at any time during the pre-harvest, harvest, and post-harvest stages. CIT can be usually found in beans, fruits, fruit and vegetable juices, herbs and spices, and dairy products, as well as red mold rice. CIT exerts nephrotoxic and genotoxic effects in both humans and animals, thereby raising concerns regarding the consumption of CIT-contaminated food and feed. Hence, to minimize the risk of CIT contamination in food and feed, understanding the incidence of CIT occurrence, its sources, and biosynthetic pathways could assist in the effective implementation of detection and mitigation measures. Therefore, this review aims to shed light on sources of CIT, its prevalence in food and feed, biosynthetic pathways, and genes involved, with a major focus on detection and management strategies to ensure the safety and security of food and feed. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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10 pages, 1349 KiB  
Review
Toxic Effects of Amanitins: Repurposing Toxicities toward New Therapeutics
by Brendan Le Daré, Pierre-Jean Ferron and Thomas Gicquel
Toxins 2021, 13(6), 417; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13060417 - 11 Jun 2021
Cited by 30 | Viewed by 6732
Abstract
The consumption of mushrooms has become increasingly popular, partly due to their nutritional and medicinal properties. This has increased the risk of confusion during picking, and thus of intoxication. In France, about 1300 cases of intoxication are observed each year, with deaths being [...] Read more.
The consumption of mushrooms has become increasingly popular, partly due to their nutritional and medicinal properties. This has increased the risk of confusion during picking, and thus of intoxication. In France, about 1300 cases of intoxication are observed each year, with deaths being mostly attributed to Amanita phalloides poisoning. Among amatoxins, α- and β-amanitins are the most widely studied toxins. Hepatotoxicity is the hallmark of these compounds, leading to hepatocellular failure within three days of ingestion. The toxic mechanisms of action mainly include RNA polymerase II inhibition and oxidative stress generation, leading to hepatic cell apoptosis or necrosis depending on the doses ingested. Currently, there is no international consensus concerning Amanita phalloides poisoning management. However, antidotes with antioxidant properties remain the most effective therapeutics to date suggesting the predominant role of oxidative stress in the pathophysiology. The partially elucidated mechanisms of action may reveal a suitable target for the development of an antidote. The aim of this review is to present an overview of the knowledge on amanitins, including the latest advances that could allow the proposal of new innovative and effective therapeutics. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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14 pages, 392 KiB  
Review
Toxic Effect of Aflatoxins in Dogs Fed Contaminated Commercial Dry Feed: A Review
by Lizbeth Martínez-Martínez, Arturo G. Valdivia-Flores, Alma Lilian Guerrero-Barrera, Teódulo Quezada-Tristán, Erika Janet Rangel-Muñoz and Raúl Ortiz-Martínez
Toxins 2021, 13(1), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13010065 - 15 Jan 2021
Cited by 13 | Viewed by 5450
Abstract
Since its first patent (1897), commercial dry feed (CDF) for dogs has diversified its formulation to meet the nutritional needs of different breeds, age, or special conditions and establish a foundation for integration of these pets into urban lifestyles. The risk of aflatoxicosis [...] Read more.
Since its first patent (1897), commercial dry feed (CDF) for dogs has diversified its formulation to meet the nutritional needs of different breeds, age, or special conditions and establish a foundation for integration of these pets into urban lifestyles. The risk of aflatoxicosis in dogs has increased because the ingredients used to formulate CDF have also proliferated, making it difficult to ensure the quality required of each to achieve the safety of the entire CDF. This review contains a description of the fungi and aflatoxins detected in CDF and the ingredients commonly used for their formulation. The mechanisms of action and pathogenic effects of aflatoxins are outlined; as well as the clinical findings, and macroscopic and microscopic lesions found in aflatoxicosis in dogs. In addition, alternatives for diagnosis, treatment, and control of aflatoxins (AF) in CDF are analyzed, such as biomarkers of effect, improvement of blood coagulation, rate of elimination of AF, control of secondary infection, protection of gastric mucosa, reduction of oxidative stress, use of chemo-protectors, sequestrants, grain-free CDF, biocontrol, and maximum permitted limits, are also included. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)

Other

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26 pages, 1627 KiB  
Systematic Review
Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review
by Carolyn W. Kinkade, Zorimar Rivera-Núñez, Ludwik Gorcyzca, Lauren M. Aleksunes and Emily S. Barrett
Toxins 2021, 13(6), 373; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13060373 - 24 May 2021
Cited by 21 | Viewed by 3821
Abstract
Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has [...] Read more.
Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN’s synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000–2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified. Full article
(This article belongs to the Special Issue Toxic Effect of Mycotoxins)
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