Study on the developmental, behavioral toxicity, and toxicological mechanism of the antidepressant drug venlafaxine and its active metabolites in zebrafish.

This article investigates the toxicological effects of the bicyclic antidepressant venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) on zebrafish (Danio rerio) as a model aquatic organism. The study found that environmentally relevant concentrations of VEN and ODV caused developmental toxicity in zebrafish embryos, including reduced hatching rates, increased mortality, growth inhibition, and morphological abnormalities. In adult zebrafish, both compounds accumulated primarily in the liver, followed by the brain and intestines, inducing oxidative stress and significant DNA hypomethylation by inhibiting DNA methyltransferase activity, particularly affecting the dnmt1 gene. Venlafaxine exhibited stronger toxic effects and greater impact on DNA methyltransferase 1 conformation than ODV, highlighting potential ecological risks of antidepressant residues in aquatic environments.