Effects of Mixed Exposure to Bisphenol F (BPF) and Perfluorooctane Sulfonic Acid (PFOS) on Hepatotoxicity and Lipid Metabolism in Zebrafish

Background: Chemicals such as bisphenols and perfluorinated compounds exist mixed in surrounding water, but the toxicity of such mixtures is not well known.Objectives: This study investigated the effects, both individually and in mixture, of bisphenol F (BPF) and perfluorooctane sulfonic acid (PFOS) on the liver toxicity and lipid metabolism of zebrafish.Methods: Zebrafish embryos were exposed to single and binary mixture of BPF (0.03~300 μg/L) and PFOS (0.01~100 μg/L) for 96 hours.Survival and growth endpoints were observed daily.To investigate liver toxicity, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the transcription of genes related to the peroxisome proliferator-activated receptor (PPAR), endoplasmic reticulum stress (ERS), and apoptosis were all evaluated.To explain the toxic mechanism of increased hepatotoxicity that occurs when BPF and PFOS are mixed, changes in the expression of the cytochrome P450 3a65 (cyp3a65) gene were measured.Results: A significant decrease in body length was observed in zebrafish larvae exposed to 30 and 300 μg/ L of BPF, 100 μg/L of PFOS, and the mixture.The activities of ALT were significantly increased in larvae exposed to BPF.Enzyme activities were well supported by the regulation of pparαa, chop, eif2a, baxa, bcl2a, and casp genes.When zebrafish were co-exposed to BPF and PFOS, the expression of the cyp3a65 gene was significantly reduced, while the levels of ALT and AST were increased.These results suggest that PFOS could increase the hepatotoxicity of BPF that depends on the CYP metabolism for its elimination. Conclusions:The results of this study indicated that BPF can induce hepatotoxicity and interfere with lipid metabolism, and PFOS increases the hepatotoxicity of BPF by inhibiting CYP metabolism.Combined contamination of BPF and PFOS may be a potentially hazardous factor, and further investigation is needed for risk assessment.