Tissue distribution and endocrine disruption effects of chronic exposure to pharmaceuticals and personal care products mixture at environmentally relevant concentrations in zebrafish

Pharmaceuticals and personal care products (PPCPs) as emerging contaminants are ubiquitously present in the aquatic environment. Using in vivo and in silico techniques, this study aims to elucidate tissue distribution and endocrine disruption effects of chronic exposure (120 days) to PPCP mixture at environmentally relevant concentrations (ERCs) in adult zebrafish. Results from UHPLC-MS/MS analyses showed elevated distribution of PPCPs in zebrafish tissues in the order of liver > gonad > brain. Upregulation of steroid hormone receptors, both gonadotropin, and steroidogenic genes perturb the HPG axis pathway in females, while male fish exhibited significantly downregulated expressions of vtg, cyp17, and 17 beta hsd genes with inhibited fecundity. The Spearman correlation indicated a significant positive relationship between PPCPs bioaccumulation and mRNA levels of HPG axis genes. In silico molecular docking (MD) revealed specific amino acid residues of PPCPs binding with zebrafish estrogen receptors. Furthermore, the strongest binding energies of sulfamethoxazole, carbamazepine, and triclosan were discovered in er alpha and er beta estrogen receptors, confirming PPCPs' xenoestrogenic behavior. To summarize, chronic exposure to ERCs resulted in a high accumulation of PPCPs in the liver and gonad tissues of adult zebrafish, as well as associated perturbed genetic responses. As a result, strict environmental regulations for the disposal of PPCPs should be ensured to protect ecological and public health.

Automated summary

Chronic exposure to PPCP mixtures at environmentally relevant concentrations resulted in high accumulation in liver and gonadal tissues of adult zebrafish, leading to perturbed genetic responses and disruption of the HPG axis pathway. In silico molecular docking revealed specific amino acid residues of PPCPs binding with estrogen receptors, confirming their xenoestrogenic behavior. Strict environmental regulations for the disposal of PPCPs are crucial to protect ecological and public health.