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Toxins
Special Issues
Effects of Single and Combined Mycotoxins
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Effects of Single and Combined Mycotoxins

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

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 22984

Special Issue Editor

Prof. Dr. Maja Šegvić Klarić

E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39, 10000 Zagreb, Croatia
Interests: mycology and mycotoxicology

Special Issue Information

Dear colleagues,

Fungi from the Aspergillus, Fusarium, and Penicillium genera are principal producers of mycotoxins that contaminate foodstuffs worldwide. The mycotoxin producers can co-occur in food substrates, and some species can simultaneously produce several mycotoxins, altogether elevating the risk of human and animal co-exposure to multiple mycotoxins. From a public health point of view, the most important foodborne mycotoxins are aflatoxins (AFs), fumonisins (FBs), trichothecenes (including deoxynivalenol (DON) and T-2 and HT-2 toxins), ochratoxin A (OTA), patulin (PAT), and zearalenone (ZEN). The maximum levels of the major mycotoxins have been set in the legislation of many countries and trade zones over the world; in the European Union, the legislation has been harmonized. Analytical methods based on liquid chromatography tandem mass spectrometry (LC-MS/MS) have enabled multiple mycotoxin detection, including major mycotoxins, masked and modified mycotoxins (e.g., DON and ZEN derivates), as well as emerging mycotoxins (enniatins-ENN, beauvericin-BEA, and fusaproliferin-FUS, and moniliformin-MON). An increasing number of publications in recent years have pointed out that binary, tertiary, and multiple mycotoxin mixtures in vitro and in vivo could result in interaction effects classified into three major types: antagonistic, additive, and synergistic. The type of interactions is influenced by multiple parameters, including the type of mycotoxin in the mixture and their concentration, duration of exposure, type of biological experimental model, toxicological endpoint, and mathematical model used to evaluate mycotoxin interaction. This Special Issue of Toxins aims to gather contributions of original research or review papers that will indicate different perspectives and addressing the problems in exposure risk assessment to mycotoxins mixtures.

Prof. Maja Šegvić Klarić
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a double-blind 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 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mycotoxin mixtures
  • mycotoxin interactions
  • combined toxicity
  • additivity
  • antagonism
  • synergy
  • cell lines
  • human and animal health

Published Papers (6 papers)

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Research

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12 pages, 1069 KiB  
Article
Impact of Mycotoxin Contaminations on Aquatic Organisms: Toxic Effect of Aflatoxin B1 and Fumonisin B1 Mixture
by Davide Di Paola, Carmelo Iaria, Fabiano Capparucci, Alessia Arangia, Rosalia Crupi, Salvatore Cuzzocrea, Nunziacarla Spanò, Enrico Gugliandolo and Alessio Filippo Peritore
Toxins 2022, 14(8), 518; https://doi.org/10.3390/toxins14080518 - 29 Jul 2022
Cited by 22 | Viewed by 3716
Abstract
(1) Background: Multiple contaminations of several mycotoxins have been detected in human and veterinary food and feed worldwide. To date, a number of studies on the combined effects of mycotoxins have been conducted on cell and animal models, but very limited studies have [...] Read more.
(1) Background: Multiple contaminations of several mycotoxins have been detected in human and veterinary food and feed worldwide. To date, a number of studies on the combined effects of mycotoxins have been conducted on cell and animal models, but very limited studies have been done on aquatic organisms. (2) The purpose of the present study was to evaluate the combined toxic effects of Aflatoxin B1 (AFB1) and Fumonisin B1 (FB1) on zebrafish (Danio rerio) embryos. (3) Results: Our results showed that the combination of AFB1 and FB1 at nontoxic concentrations exerted a negative effect on the lethal endpoints analyzed, such as survival, hatching, and heart rate. In addition, the mixture of mycotoxins caused an increase in the levels of enzymes and proteins involved in the antioxidant process, such as superoxide dismutase (SOD) and catalase (CAT), both in terms of protein levels and gene expression, as well as an increase in the levels of the detoxification enzymes glutathione s-transferases (GST) and cytochromes P450 (CYP450). Furthermore, we showed that the mycotoxin mixture induced an increase in pro-apoptotic proteins such as bax and caspase 3, and at the same time reduced the gene expression of the anti-apoptotic bcl-2 protein. Finally, a significant decrease in thyroid function was observed in terms of triiodothyronine (T3), thyroxine (T4), and vitellogenin (VTG) levels. (4) Conclusion: We can say that the mixture of mycotoxins carries a greater risk factor than individual presences. There is a greater need for effective detoxification methods to control and reduce the toxicity of multiple mycotoxins and reduce the toxicity of multiple mycotoxins in feed and throughout the food chain. Full article
(This article belongs to the Special Issue Effects of Single and Combined Mycotoxins)
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13 pages, 2364 KiB  
Article
Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins
by Sanja Dabelić, Domagoj Kifer, Daniela Jakšić, Nevenka Kopjar and Maja Šegvić Klarić
Toxins 2021, 13(7), 464; https://doi.org/10.3390/toxins13070464 - 30 Jun 2021
Cited by 3 | Viewed by 2331
Abstract
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are structurally related mycotoxins with cytotoxic and genotoxic properties. In the present study, we hypothesized that DNA damage induced by non-cytotoxic concentrations of single and combined mycotoxins could alter the phosphorylation of the checkpoint proteins Chk2 and FANCD2 [...] Read more.
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are structurally related mycotoxins with cytotoxic and genotoxic properties. In the present study, we hypothesized that DNA damage induced by non-cytotoxic concentrations of single and combined mycotoxins could alter the phosphorylation of the checkpoint proteins Chk2 and FANCD2 (ELISA) in HepG2 and A549 cells. The cytotoxic potential (MTT test) of single and combined STC and 5-M-STC, the nature of their interaction (additivity, antagonism, or synergy) and DNA damage level (alkaline comet assay) in HepG2 and A549 cells were also investigated. All experiments were performed after 24 h of mycotoxin treatment. 5-M-STC was 10-folds more cytotoxic than STC to both HepG2 and A549 cells. Both mycotoxins are genotoxic to HepG2 and A549 cells by inducing both double and single DNA strand breaks that activate Chk2 (especially in HepG2 cells) but not the FANCD2 protein. STC exerted higher genotoxic potential than 5-M-STC in HepG2 and A549 cells when both toxins were applied individually at the same concentration. Dual combinations of non-cytotoxic mycotoxin concentrations showed additive to antagonizing cytotoxic and genotoxic effects. The absence and low activation of checkpoint proteins during prolonged exposure to non-cytotoxic concentrations of STC and 5-M-STC could support cell proliferation and carcinogenesis. Full article
(This article belongs to the Special Issue Effects of Single and Combined Mycotoxins)
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23 pages, 8348 KiB  
Article
Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis
by Yanan Gao, Xiaoyu Bao, Lu Meng, Huimin Liu, Jiaqi Wang and Nan Zheng
Toxins 2021, 13(3), 184; https://doi.org/10.3390/toxins13030184 - 2 Mar 2021
Cited by 24 | Viewed by 2781
Abstract
With the growing diversity and complexity of diet, humans are at risk of simultaneous exposure to aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1), which are well-known contaminants in dairy and other agricultural products worldwide. The intestine represents the first barrier against external contaminants; [...] Read more.
With the growing diversity and complexity of diet, humans are at risk of simultaneous exposure to aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1), which are well-known contaminants in dairy and other agricultural products worldwide. The intestine represents the first barrier against external contaminants; however, evidence about the combined effect of AFB1 and AFM1 on intestinal integrity is lacking. In vivo, the serum biochemical parameters related to intestinal barrier function, ratio of villus height/crypt depth, and distribution pattern of claudin-1 and zonula occluden-1 were significantly affected in mice exposed to 0.3 mg/kg b.w. AFB1 and 3.0 mg/kg b.w. AFM1. In vitro results on differentiated Caco-2 cells showed that individual and combined AFB1 (0.5 and 4 μg/mL) and AFM1 (0.5 and 4 μg/mL) decreased cell viability and trans-epithelial electrical resistance values as well as increased paracellular permeability of fluorescein isothiocyanate-dextran in a dose-dependent manner. Furthermore, AFM1 aggravated AFB1-induced compromised intestinal barrier, as demonstrated by the down-regulation of tight junction proteins and their redistribution, particularly internalization. Adding the inhibitor chlorpromazine illustrated that clathrin-mediated endocytosis partially contributed to the compromised intestinal integrity. Synergistic and additive effects were the predominant interactions, suggesting that these toxins are likely to have negative effects on human health. Full article
(This article belongs to the Special Issue Effects of Single and Combined Mycotoxins)
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10 pages, 699 KiB  
Article
Mitigation Effects of Bentonite and Yeast Cell Wall Binders on AFB1, DON, and OTA Induced Changes in Laying Hen Performance, Egg Quality, and Health
by Ling Zhao, Yue Feng, Jing-Tao Wei, Meng-Xiang Zhu, Lei Zhang, Jia-Cai Zhang, Niel Alexander Karrow, Yan-Ming Han, Yuan-Yuan Wu, Yu-Ming Guo and Lv-Hui Sun
Toxins 2021, 13(2), 156; https://doi.org/10.3390/toxins13020156 - 17 Feb 2021
Cited by 17 | Viewed by 3517
Abstract
The objective of this study was to evaluate the efficacy of mycotoxin binders in reducing the adverse effects of co-occurring dietary aflatoxin B1 (AFB1), deoxynivalenol (DON) and ochratoxin A (OTA) on laying hens. Three hundred and sixty 26-week-old Roman laying [...] Read more.
The objective of this study was to evaluate the efficacy of mycotoxin binders in reducing the adverse effects of co-occurring dietary aflatoxin B1 (AFB1), deoxynivalenol (DON) and ochratoxin A (OTA) on laying hens. Three hundred and sixty 26-week-old Roman laying hens were randomly allocated into four experimental groups with 10 replicates of nine birds each. The four groups received either a basal diet (BD; Control), a BD supplemented with 0.15 mg/kg AFB1 + 1.5 mg/kg DON + 0.12 mg/kg OTA (Toxins), a BD + Toxins with Toxo-HP binder (Toxins + HP), or a BD + Toxins with TOXO XL binder (Toxins + XL) for 12 weeks. Compared to the control, dietary supplementation of mycotoxins decreased (P < 0.10) total feed intake, total egg weight, and egg-laying rate, but increased feed/egg ratio by 2.5–6.1% and mortality during various experimental periods. These alterations induced by mycotoxins were alleviated by supplementation with both TOXO HP and XL binders (P < 0.10). Furthermore, dietary mycotoxins reduced (P < 0.05) eggshell strength by 12.3% and caused an accumulation of 249 μg/kg of DON in eggs at week 12, while dietary supplementation with TOXO HP or XL mitigated DON-induced changes on eggshell strength and prevented accumulation of DON in eggs (P < 0.05). Moreover, dietary mycotoxins increased relative liver weight, but decreased spleen and proventriculus relative weights by 11.6–22.4% (P < 0.05). Mycotoxin exposure also increased alanine aminotransferase activity and reduced immunoglobulin (Ig) A, IgM, and IgG concentrations in serum by 9.2–26.1% (P < 0.05). Additionally, mycotoxin exposure induced histopathological damage and reduced villus height, villus height/crypt depth, and crypt depth in duodenum, jejunum and (or) ileum (P < 0.05). Notably, most of these histological changes were mitigated by supplementation with both TOXO HP and XL (P < 0.05). In conclusion, the present study demonstrated that the mycotoxin binders TOXO HP and XL can help to mitigate the combined effects of AFB1, DON, and OTA on laying hen performance, egg quality, and health. Full article
(This article belongs to the Special Issue Effects of Single and Combined Mycotoxins)
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15 pages, 347 KiB  
Article
Comparative Toxigenicity and Associated Mutagenicity of Aspergillus fumigatus and Aspergillus flavus Group Isolates Collected from the Agricultural Environment
by Caroline Lanier, David Garon, Natacha Heutte, Valérie Kientz and Véronique André
Toxins 2020, 12(7), 458; https://doi.org/10.3390/toxins12070458 - 17 Jul 2020
Cited by 4 | Viewed by 2347
Abstract
The mutagenic patterns of A. flavus, A. parasiticus and A. fumigatus extracts were evaluated. These strains of toxigenic Aspergillus were collected from the agricultural environment. The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous [...] Read more.
The mutagenic patterns of A. flavus, A. parasiticus and A. fumigatus extracts were evaluated. These strains of toxigenic Aspergillus were collected from the agricultural environment. The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous metabolic activation system). These data were compared with the mutagenicity of the corresponding pure mycotoxins tested alone or in reconstituted mixtures with equivalent concentrations, in order to investigate the potential interactions between these molecules and/or other natural metabolites. At least 3 mechanisms are involved in the mutagenic response of these aflatoxins: firstly, the formation of AFB1-8,9-epoxide upon addition of S9mix, secondly the likely formation of oxidative damage as indicated by significant responses in TA102, and thirdly, a direct mutagenicity observed for higher doses of some extracts or associated mycotoxins, which does not therefore involve exogenously activated intermediates. Besides the identified mycotoxins (AFB1, AFB2 and AFM1), additional “natural” compounds contribute to the global mutagenicity of the extracts. On the other hand, AFB2 and AFM1 modulate negatively the mutagenicity of AFB1 when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of “natural” mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli. Full article
(This article belongs to the Special Issue Effects of Single and Combined Mycotoxins)

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42 pages, 974 KiB  
Review
The Compromised Intestinal Barrier Induced by Mycotoxins
by Yanan Gao, Lu Meng, Huimin Liu, Jiaqi Wang and Nan Zheng
Toxins 2020, 12(10), 619; https://doi.org/10.3390/toxins12100619 - 28 Sep 2020
Cited by 69 | Viewed by 7504
Abstract
Mycotoxins are fungal metabolites that occur in human foods and animal feeds, potentially threatening human and animal health. The intestine is considered as the first barrier against these external contaminants, and it consists of interconnected physical, chemical, immunological, and microbial barriers. In this [...] Read more.
Mycotoxins are fungal metabolites that occur in human foods and animal feeds, potentially threatening human and animal health. The intestine is considered as the first barrier against these external contaminants, and it consists of interconnected physical, chemical, immunological, and microbial barriers. In this context, based on in vitro, ex vivo, and in vivo models, we summarize the literature for compromised intestinal barrier issues caused by various mycotoxins, and we reviewed events related to disrupted intestinal integrity (physical barrier), thinned mucus layer (chemical barrier), imbalanced inflammatory factors (immunological barrier), and dysfunctional bacterial homeostasis (microbial barrier). We also provide important information on deoxynivalenol, a leading mycotoxin implicated in intestinal dysfunction, and other adverse intestinal effects induced by other mycotoxins, including aflatoxins and ochratoxin A. In addition, intestinal perturbations caused by mycotoxins may also contribute to the development of mycotoxicosis, including human chronic intestinal inflammatory diseases. Therefore, we provide a clear understanding of compromised intestinal barrier induced by mycotoxins, with a view to potentially develop innovative strategies to prevent and treat mycotoxicosis. In addition, because of increased combinatorial interactions between mycotoxins, we explore the interactive effects of multiple mycotoxins in this review. Full article
(This article belongs to the Special Issue Effects of Single and Combined Mycotoxins)
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