Hepatotoxicity caused by methylparaben in adult zebrafish

•Subchronic exposure to methylparaben induced hepatocyte vacuolization in zebrafish.•Methylparaben exposure disrupted redox homeostasis in zebrafish liver.•Systemic disturbances in lipid metabolism were noted after methylparaben exposure.•Fingerprint of metabolome in liver was perturbed by methylparaben.•Synthesis of primary bile acid was inhibited in methylparaben-exposed liver. Parabens are a class of aquatic pollutants of emerging concern, among which methylparaben (MeP) causes severe pollution worldwide. However, aquatic toxicology of MeP remains largely unknown, which hinders ecological risk evaluation. In the present study, adult zebrafish were exposed to environmentally realistic concentrations (0, 1, 3, and 10 μg/L) of MeP for 28 days, with objectives to reveal the hepatotoxicity based on transcriptional, biochemical, metabolomics, and histopathological evidences. The results showed that MeP subchronic exposure induced the occurrence of hepatocellular vacuolization in zebrafish. The most severe symptom was noted in 10 μg/L MeP-exposed female liver, which was characterized by rupture of cell membrane and small nuclei. In addition, MeP exposure disturbed the balance between oxidative stress and antioxidant capacity. Lipid metabolism dynamics across gut, blood, and liver system were significantly dysregulated after MeP exposure by altering the transcriptions of lipid nuclear receptors and concentrations of key metabolites. Metabolomic profiling of MeP-exposed liver identified differential metabolites mainly belonging to fatty acyls, steroids, and retinoids. In particular, hepatic concentration of cortisol was increased in male liver by MeP pollutant, implying the activation of stress response. Exposure to MeP also inhibited the synthesis and conjugation of primary bile acid (e.g., 7-ketolithocholic acid and taurochenodeoxycholic acid) in female liver. Furthermore, degradation of biologically active molecules, including retinoic acid and estradiol, was enhanced in the liver by MeP. Overall, the present study highlights the hepatotoxicity caused by MeP pollutant even at environmentally realistic concentrations, which necessitates an urgent and accurate risk assessment. [Display omitted]