Hepatotoxicity caused by methylparaben in adult zebrafish

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 mu g/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 mu g/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 meta-bolism 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 con-centrations, which necessitates an urgent and accurate risk assessment.

Automated summary

This study investigates the hepatotoxicity of methylparaben (MeP) in adult zebrafish exposed to environmentally realistic concentrations of MeP. The results show that MeP exposure induces hepatocellular vacuolization in zebrafish and disrupts the balance between oxidative stress and antioxidant capacity. MeP exposure also dysregulates lipid metabolism and alters the concentrations of key metabolites. Overall, this study highlights the hepatotoxic effects of MeP even at environmentally realistic concentrations.