Global liver proteomic analysis of Wistar rats chronically exposed to low-levels of bisphenol A and S

Abstract Exposure to bisphenol A (BPA) and bisphenol S (BPS) has been associated with the development of metabolic disorders, such as obesity, dyslipidemias, and nonalcoholic fatty liver disease. Nonetheless, the associated mechanisms are still not fully understood. BPS is being used with no restrictions to replace BPA, which increases the concern regarding its safety and claims for further investigation on its potential mechanisms of toxicity. The present study aims to access liver molecular disturbances which could be associated with systemic metabolic disorders following exposure to BPA or BPS. Therefore, body weight gain and serum biochemical parameters were measured in male Wistar rats chronically exposed to 50 or 500 µg/kg/day of BPA or BPS, while an extensive evaluation of liver protein expression changes was conducted after exposure to 50 µg/kg/day of both compounds. Exposure to the lowest dose of BPA led to the development of hyperglycemia and hypercholesterolemia, while the BPS lowest dose led to the development of hypertriglyceridemia. Besides, exposure to 500 µg/kg/day of BPS significantly increased body weight gain and LDL-cholesterol levels. Hepatic proteins differentially expressed in BPA and BPS-exposed groups compared to the control group were mostly related to lipid metabolism and synthesis, with upregulation of glucokinase activity-related sequence 1 (1.8-fold in BPA and 2.4-fold in BPS), which is involved in glycerol triglycerides synthesis, and hydroxymethylglutaryl-CoA synthase cytoplasmic (2-fold in BPS), an enzyme involved in mevalonate biosynthesis. Essential mitochondrial proteins of the electron transport chain were upregulated after exposure to both contaminants. Also, BPA and BPS dysregulated expression of liver antioxidant enzymes, which are involved in cellular reactive oxygen species detoxification. Altogether, the results of the present study contribute to expand the scientific understanding of how BPA and BPS lead to the development of metabolic disorders and reinforce the risks associated with exposure to these contaminants.