A novel toxic effect of foodborne trichothecenes: The exacerbation of genotoxicity

Garofalo, Marion; Payros, Delphine; Pénary, Marie; Oswald, Éric; Nougayrède, Jean-Philippe; Oswald, Isabelle P.

doi:10.1016/j.envpol.2022.120625

Cited by 12 publications

(2 citation statements)

References 66 publications

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“…Although deoxynivalenol is not genotoxic by itself, it has recently been shown that this toxin exacerbates the genotoxicity induced by model or bacterial genotoxins. In addition, other trichothecenes, namely, T-2 toxin, diacetoxyscirpenol, nivalenol, fusarenon-X, and the newly discovered NX toxin, were also reported as compounds able to exacerbate the DNA damage inflicted by various genotoxins [ 42 ]. In addition, in the study reported by Yang et al [ 43 ], deoxynivalenol was able to cause damage to the membrane, the chromosomes, and the DNA at all times of culture in human peripheral blood lymphocytes, thus concluding that deoxynivalenol potentially triggers genotoxicity in human lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

MicotoXilico: An Interactive Database to Predict Mutagenicity, Genotoxicity, and Carcinogenicity of Mycotoxins

Tolosa,

Serrano Candelas,

Vallés Pardo

et al. 2023

Toxins

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Mycotoxins are secondary metabolites produced by certain filamentous fungi. They are common contaminants found in a wide variety of food matrices, thus representing a threat to public health, as they can be carcinogenic, mutagenic, or teratogenic, among other toxic effects. Several hundreds of mycotoxins have been reported, but only a few of them are regulated, due to the lack of data regarding their toxicity and mechanisms of action. Thus, a more comprehensive evaluation of the toxicity of mycotoxins found in foodstuffs is required. In silico toxicology approaches, such as Quantitative Structure–Activity Relationship (QSAR) models, can be used to rapidly assess chemical hazards by predicting different toxicological endpoints. In this work, for the first time, a comprehensive database containing 4360 mycotoxins classified in 170 categories was constructed. Then, specific robust QSAR models for the prediction of mutagenicity, genotoxicity, and carcinogenicity were generated, showing good accuracy, precision, sensitivity, and specificity. It must be highlighted that the developed QSAR models are compliant with the OECD regulatory criteria, and they can be used for regulatory purposes. Finally, all data were integrated into a web server that allows the exploration of the mycotoxin database and toxicity prediction. In conclusion, the developed tool is a valuable resource for scientists, industry, and regulatory agencies to screen the mutagenicity, genotoxicity, and carcinogenicity of non-regulated mycotoxins.

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Section: Discussionmentioning

confidence: 99%

MicotoXilico: An Interactive Database to Predict Mutagenicity, Genotoxicity, and Carcinogenicity of Mycotoxins

Tolosa,

Serrano Candelas,

Vallés Pardo

et al. 2023

Toxins

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“…Several epidemiological studies conducted on adults and children have reported that DON and its metabolites were detected in more than 80% of urine samples from France, Spain Belgium, Germany, China, and the United Kingdom. − Reportedly, there exists a range of 7.0 to 120.0 g/L for the average concentration of DON and DON metabolites in human urine, with 12–40% of the samples surpassing the permissible tolerated daily intake . The absorption of DON can lead to gastroenteritis, emesis, anorexia, growth retardation, immunotoxicity, decreased reproduction, and disruption of the integrity of gut microbiota, thereby posing ongoing risks to public health. , Numerous studies have reported that DON exposure causes oxidative stress cell membrane rupture, DNA damage, and protein synthesis inhibition − …”

Section: Introductionmentioning

confidence: 99%

Deoxynivalenol Induces Drp-1-Mediated Mitochondrial Dysfunction via Elevating Oxidative Stress

Mishra,

Kapoor,

Sushma

et al. 2024

Chem. Res. Toxicol.

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Mitochondrial dysfunction is often linked to neurotoxicity and neurological diseases and stems from oxidative stress, yet effective therapies are lacking. Deoxynivalenol (DON or vomitoxin) is one of the most common and hazardous type-B trichothecene mycotoxins, which contaminates crops used for food and animal feed. Despite the abundance of preliminary reports, comprehensive investigations are scarce to explore the relationship between these fungal metabolites and neurodegenerative disorders. The present study aimed to elucidate the precise role of DON in mitochondrial dynamics and cell death in neuronal cells. Excessive mitochondrial fission is associated with the pathology of several neurodegenerative diseases. Human SH-SY5Y cells were treated with different concentrations of DON (250–1000 ng/mL). Post 24 and 48 h DON treatment, the indexes were measured as follows: generation of reactive oxygen species (ROS), ATP levels, mitochondrial membrane potential, calcium levels, and cytotoxicity in SH-SY5Y cells. The results showed that cytotoxicity, intracellular calcium levels, and ROS in the DON-treated group increased, while the ATP levels and mitochondrial membrane potential decreased in a dose-dependent manner. With increasing DON concentrations, the expression levels of P-Drp-1, mitochondrial fission proteins Mff, and Fis-1 were elevated with reduced activities of MFN1, MFN2, and OPA1, further resulting in an increased expression of autophagic marker LC3 and beclin-1. The reciprocal relationship between mitochondrial damage and ROS generation is evident as ROS can instigate structural and functional deficiencies within the mitochondria. Consequently, the impaired mitochondria facilitate the release of ROS, thereby intensifying the cycle of damage and exacerbating the overall process. Using specific hydroxyl, superoxide inhibitors, and calcium chelators, our study confirmed that ROS and Ca2+-mediated signaling pathways played essential roles in DON-induced Drp1 phosphorylation. Therefore, ROS and mitochondrial fission inhibitors could provide critical research tools for drug development in mycotoxin-induced neurodegenerative diseases.

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In vitro assessment of commercial multi-mycotoxin binders to reduce the bioavailability of emerging mycotoxins in livestock

Siri-anusornsak,

Meneely,

Greer

et al. 2023

Emerging Contaminants

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A novel toxic effect of foodborne trichothecenes: The exacerbation of genotoxicity

Cited by 12 publications

References 66 publications

MicotoXilico: An Interactive Database to Predict Mutagenicity, Genotoxicity, and Carcinogenicity of Mycotoxins

MicotoXilico: An Interactive Database to Predict Mutagenicity, Genotoxicity, and Carcinogenicity of Mycotoxins

Deoxynivalenol Induces Drp-1-Mediated Mitochondrial Dysfunction via Elevating Oxidative Stress

In vitro assessment of commercial multi-mycotoxin binders to reduce the bioavailability of emerging mycotoxins in livestock

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