Special Issue "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: 31 October 2021.

Special Issue Editor

Prof. Maja Šegvić Klarić
E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39, Zagreb 10000, 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

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Keywords

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

Published Papers (4 papers)

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Research

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Open AccessArticle
Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis
Toxins 2021, 13(3), 184; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030184 - 02 Mar 2021
Viewed by 410
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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Open AccessArticle
Mitigation Effects of Bentonite and Yeast Cell Wall Binders on AFB1, DON, and OTA Induced Changes in Laying Hen Performance, Egg Quality, and Health
Toxins 2021, 13(2), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020156 - 17 Feb 2021
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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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Open AccessArticle
Comparative Toxigenicity and Associated Mutagenicity of Aspergillus fumigatus and Aspergillus flavus Group Isolates Collected from the Agricultural Environment
Toxins 2020, 12(7), 458; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12070458 - 17 Jul 2020
Cited by 1 | Viewed by 706
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)

Review

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Open AccessReview
The Compromised Intestinal Barrier Induced by Mycotoxins
Toxins 2020, 12(10), 619; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100619 - 28 Sep 2020
Cited by 7 | Viewed by 1003
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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