Abstract

Beauvericin (BEA), a food-borne mycotoxin metabolite derived from the fungusBeauveria Bassiana, is proven to exhibit high hepatotoxicity. However, the molecular mechanism underlying BEA-induced liver damage is not fully understood. Herein, the effect of Nrf2 nuclear translocation-induced by BEA in hepatocytes was investigated. CCK8 solution was used to determine the appropriate concentrations of BEA (0, 1, 1.5 and 2 μmol/L), and BRL3A cells were then exposed to different concentrations of BEA for 12 h. Our results reveal that BEA exposure is associated with high cytotoxicity, lowered cell viability, damaged cellular morphology, and increased apoptosis rate. BEA could lead to oxidative damage through the overproduction of ROS and unbalanced redox, trigger the activation of Nrf2 signaling pathway and Nrf2 nuclear translocation for transcriptional activation of downstream antioxidative genes. Additionally, BEA treatment upregulated the expression of autophagy-related proteins (LC3, p62, Beclin1, and ATG5) indicating a correlation between Nrf2 activation and autophagy, which warrants further studies. Furthermore, ML385, an Nrf2 inhibitor, partially ameliorated BEA-induced cell injury while CDDO, an Nrf2 activator, aggravated liver damage. The present study emphasizes the role of Nrf2 nuclear translocation in BEA-induced oxidative stress associated with the hepatotoxic nature of BEA.Keywords:beauvericin;apoptosis;oxidative stress;Nrf2;autophagyKey Contribution:The study firstly confirmed that BEA induced oxidative stress; accompanied by overproduction of ROS, Nrf2 activation and translocation to the nucleus, and initiated autophagy, which provides a novel insight into the molecular mechanism of BEA exposure-induced hepatotoxicity.