Elucidating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 cells based on respirometry and transcriptome analyses

Abstract

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are two toxic mycotoxins widely found in food contaminants, and known for their hepatotoxicity in human. However, their combined toxicity still needs to be deeply investigated especially for their harmful effect. Therefore, the current work aimed at investigating the (combined) effect of AFB1 and FB1 on mitochondrial and glycolytic activity of HepG2 cell line, a well-recognized in vitro model system to study liver cell function. In our previous work, we studied the impact of a short term exposure to different doses of AFB1, FB1, and their binary mixture (MIX) on the bioenergetic status of HepG2 cells. Seahorse respirometry analysis revealed that the co-exposure, especially at high doses (8 μg/mL for AFB1 and 160 μg/mL for FB1), is more toxic as a result of more inhibition of all parameters of mitochondrial respiration. RNA transcriptome sequencing showed that the p53 signaling pathway, which is a major orchestrator of mitochondrial apoptosis, was differentially expressed. Moreover, the co-exposure has significantly downregulated Cx I, Cx II, Cx III, and Cx IV genes, which represent the onset of the suppressed mitochondrial respiration in HepG2 cells. It was found that FB1 is contributed more to the MIX effects than AFB1.