Bisphenol A Alters the Expression of Genes Involved in Lipogenesis, Inflammation, and Oxidative Stress in the Liver...

Background: Bisphenol A (BPA) is a widespread environmental endocrine disruptor associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its short-term effects at low, environmentally relevant concentrations are still poorly understood. Methods: Adult zebrafish were exposed to 5, 20, or 100 µg/L BPA for 48 h, 7, or 14 days in a pilot test. The lowest effective condition (20 µg/L for 7 days) was selected for a complete experiment. Fish were divided into two groups: control and BPA-exposed (n = 50/group). After exposure, livers were collected for histological (HE, Oil Red O, Nile Red) and molecular (RT-qPCR) analyses. Results: Exposure to 20 µg/L BPA for 7 days induced moderate to severe hepatic steatosis, characterized by vacuolization, hepatocyte ballooning, and lipid accumulation. Gene expression analysis showed upregulation of fasn (fatty acid synthase), acc1 (acetyl-CoA carboxylase 1), srebp-1c (sterol regulatory element-binding protein 1c), nfkb (nuclear factor kappa B), il-6 (interleukin-6), gpx1 (glutathione peroxidase 1), sod (superoxide dismutase), cyp1a (cytochrome P450 1A), and cyp2ad2 (cytochrome P450 2AD2), while adipor2 (adiponectin receptor 2) and gpx4 (glutathione peroxidase 4) were downregulated (decreased activity). Conclusions: Short-term exposure to a low, environmentally relevant concentration of BPA was sufficient to trigger hepatic steatosis in zebrafish. These effects were associated with enhanced lipogenesis, inflammation, oxidative imbalance, and altered xenobiotic metabolism, suggesting that even brief, low-dose BPA exposure may contribute to early events in MASLD pathogenesis.