Metabolic toxicity of PAHs in Ruditapes philippinarum: Metabolic pathways and hepatotoxicity.

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that exhibit high bioaccumulation and toxicity, posing a significant threat to marine ecosystems. This study integrated transcriptomics, computational modeling, and experimental validation to elucidate the detoxification metabolism and hepatotoxicity of a PAHs mixture (phenanthrene: chrysene: benzo[a]pyrene = 1:1:1) in the Manila clam (Ruditapes philippinarum). PAHs exposure activated detoxification genes via aryl hydrocarbon receptor and HR96-like pathways, with additional modulation through neurotransmitter-mediated NF-κB and tyrosine kinase signaling. Phase I (e.g., CYP1A1, CYP3A4) and Phase II enzymes were upregulated, yet persistent reactive oxygen species accumulation caused macromolecular damage. Females exhibited lower detoxification but greater oxidative stress than males. Chronic oxidative injury induced liver impairment, probably accompanied by inflammation and fibrosis. These findings reveal sex-dependent toxicological responses and provide mechanistic insights for ecological risk assessment and biomarker development in marine pollution monitoring.