Percorrer por autor "Vilela, Rita Sofia"
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- From Food to Humans: The Toxicological Effects of Alternaria Mycotoxins in the Liver and ColonPublication . Vilela, Rita Sofia; Pina-Martins, Francisco; Ventura, CéliaAlternaria mycotoxins represent a significant and emerging concern in the field of food safety due to their widespread occurrence in diverse food and feed commodities, including cereals, tomatoes, oilseeds, and dried fruits. Among these, alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA), and altertoxin-I (ATX-I) are the most frequently detected, often co-occurring at varying concentrations, thereby increasing the complexity of exposure and risk assessment. The gastrointestinal tract (GIT) is a crucial target of these toxins, as well as the liver, particularly considering its detoxifying role. Nevertheless, despite being a source of possible gastrointestinal and hepatic toxicity, there is still scarce data on the toxicokinetics of Alternaria toxins, on their mode of action, and respective toxic effects. To date, in vitro studies have shown that different Alternaria mycotoxins exhibit diverse toxicological effects, which may be dependent on their chemical structure. AOH and ATX-I have shown genotoxicity and cytotoxicity, mainly through interaction with the DNA and apoptosis, respectively. Tentoxin (TEN) has displayed hepatotoxic potential via impairment of detoxification pathways, and altenuene (ALT) has revealed lower toxicity. In vivo, AME and ATX-II revealed genotoxicity, while AOH and ATX-I showed context-dependent variability in their effects. Altogether, this review emphasizes that there is still a great lack of knowledge on these mycotoxins and an urgent need for more comprehensive toxicological and occurrence data to support proper risk assessment and, ultimately, regulatory decision-making.
- Genotoxic effects of Alternaria mycotoxins in human liver HepG2 cellsPublication . Ventura, Célia; Vilela, Rita Sofia; Guerreiro, Beatriz; Louro, Henriqueta; Silva, Maria JoãoObjective: Mycotoxins are natural toxic compounds produced by filamentous fungi as secondary metabolites. Human exposure to mycotoxins occurs predominantly through ingestion of contaminated food, and have been associated with nephrotoxicity, hepatotoxicity, immunotoxicity, carcinogenicity, and teratogenicity. Alternaria mycotoxins are produced by black moulds of the genus Alternaria, which are common plant pathogens and saprophytes widely distributed in the environment. However, limited toxicological data exists on Alternaria mycotoxins. Within the scope of the European Partnership for the Assessment of Risks from Chemicals (PARC; https://www.eu-parc.eu/) these toxins were considered as priority substances, and several studies are underway with the aim of filling knowledge gaps regarding their genotoxicity, among other toxic effects. Methods: Genotoxicity was evaluated using the In Vitro Mammalian Cell Micronucleus Assay with cytokinesis block (CBMN) according to the OECD TG 487. HepG2 liver cells were exposed for 48 h to a concentration-range of each Alternaria mycotoxin following dose-range finding based on cytotoxicity testing (MTT assay). Vinblastine was used as a positive control. Results: All tested mycotoxins were cytotoxic in the MTT assay and genotoxic in the CBMN assay. In addition to the significant increase in micronucleated binucleated cells, some mycotoxins also induced a significant increase in other nuclear anomalies in HepG2 cells, showing a dose-response relationship. Conclusions: These results indicate that the studied Alternaria mycotoxins induce chromosomal damage, which can lead to genomic instability, a key driver in cancer. Therefore, this study contributes to PARC objectives, providing critical toxicological data for their hazard assessment following human oral exposure. The data will contribute to support their risk assessment and management by regulators and policy makers in order to protect human health from these emerging food contaminants.