Journal of Hazardous Materials · May 14, 2026

Benzo[a]pyrene induces non-alcoholic fatty liver disease by exacerbating hepatic senescence and disrupting gut-liver axis in zebrafish

By Shu Y, Hu K, Gong C et al.

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are ubiquitous environmental contaminants that may impair liver health and contribute to nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying its hepatotoxicity remain poorly understood. We aimed to evaluate the hepatotoxic risks of environmentally relevant BaP exposure and to elucidate the mechanisms contributing to NAFLD progression. After exposing zebrafish to BaP for 4 weeks, liver health was assessed by histopathology, biochemical assays, and gene expression profiling, with a focus on lipid metabolism, hepatocyte senescence, and gut-liver axis integrity. Our results demonstrated that BaP exposure induced hepatic fat accumulation and elevated TG, T-CHO, FFA, and TBA levels, associated with upregulated lipogenesis and suppressed lipid catabolism. BaP also activated the AHR signaling pathway, caused DNA damage, disrupted cell cycle regulation, and exacerbated hepatic senescence, leading to inflammation and mitochondrial dysfunction. Moreover, BaP impaired intestinal barrier function, induced gut microbiota dysbiosis, and elevated serum lipopolysaccharides (LPS), which activated its reception and downstream hepatic pathways. Our findings suggest that BaP may induce NAFLD by exacerbating liver senescence and disrupting the gut-liver axis. These results highlight overlooked liver health risks of environmental BaP and warrant further research in both mammalian models and human populations.

doi.org/10.1016/j.jhazmat.2026.142365PubMed 42139782Mechanisms