Abstract
Aflatoxin B1 (AFB1) is a natural feed and food contaminant classified as a group I carcinogen for humans. In the dairy industry, AFB1 and its derivative, AFM1, are of concern for the related economic losses and their possible presence in milk and dairy food products. Among its toxic effects, AFB1 can cause oxidative stress. Thus, dietary supplementation with natural antioxidants has been considered among the strategies to mitigate AFB1 presence and its toxicity. Here, the protective role of resveratrol (R) has been investigated in a foetal bovine hepatocyte cell line (BFH12) exposed to AFB1, by measuring cytotoxicity, transcriptional changes (RNA sequencing), and targeted post-transcriptional modifications (lipid peroxidation, NQO1 and CYP3A enzymatic activity). Resveratrol reversed the AFB1-dependent cytotoxicity. As for gene expression, when administered alone, R induced neglectable changes in BFH12 cells. Conversely, when comparing AFB1-exposed cells with those co-incubated with R+AFB1, greater transcriptional variations were observed (i.e., 840 DEGs). Functional analyses revealed that several significant genes were involved in lipid biosynthesis, response to external stimulus, drug metabolism, and inflammatory response. As for NQO1 and CYP3A activities and lipid peroxidation, R significantly reverted variations induced by AFB1, mostly corroborating and/or completing transcriptional data. Outcomes of the present study provide new knowledge about key molecular mechanisms involved in R antioxidant-mediated protection against AFB1 toxicity.
Highlights
Introduction iationsAflatoxins (AFs) are mycotoxins naturally affecting cereal grains and animal feeds around the world [1,2]
Based on the present results, and the experiments that we have previously performed on this cell model, the following conclusions can be drawn
(4) The pathways mostly affected by R pre-treatment, and driving protective mechanisms against aflatoxin B1 (AFB1) toxicity, are related to lipid biosynthetic processes, inflammation, drug metabolism, and drug transport
Summary
Aflatoxins (AFs) are mycotoxins naturally affecting cereal grains and animal feeds around the world [1,2]. They can cause various diseases and health issues in humans and farmed animals. In the latter, AFs exposure might have severe implications, such as liver damage, nutritional or immunological consequences. AFs exposure might have severe implications, such as liver damage, nutritional or immunological consequences These effects lead to decreased animal growth and productivity [3,4,5], resulting in significant economic losses [6,7]. AFB1 is biologically activated by a number of cytochromes P450 (CYPs), namely CYP1A and CYP3A, to an extremely reactive and electrophilic derivative, AFB1-8,9-epoxide (AFBO), Licensee MDPI, Basel, Switzerland
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