Resveratrol alleviates fenvalerate-induced cardiotoxicity in zebrafish larvae by inhibiting oxidative stress and apoptosis.

Fenvalerate (FEN), a widely used an agricultural type II pyrethroid pesticide, has been found in the environment and human tissues. Nevertheless, the cardiotoxicity of FEN remains poorly understood. This study aimed to explore the cardiotoxicity of FEN and the potential cardioprotective role of resveratrol (RES, a polyphenolic antioxidant) in zebrafish. In this research, zebrafish embryos were exposed to FEN at concentrations of 0, 3.5 and 7 μg/L from 4 to 96 h post fertilization (hpf) and developmental cardiotoxicity was evaluated. The findings demonstrated that FEN significantly impaired embryonic development, with lower survival and hatching success, diminished spontaneous movement, lower heart rate and body length, as well as an elevated malformation rate. FEN induced both morphological and functional abnormalities in the heart of myl7:egfp zebrafish, along with the downregulation of genes related to cardiac development. FEN also induced oxidative stress by generating excessive reactive oxygen species and disturbing antioxidant enzyme activities, thereby triggering cardiomyocyte apoptosis via upregulated apoptotic gene expression. Remarkably, these cardiotoxic effects were effectively mitigated by RES via its antioxidation, underscoring oxidative stress and apoptosis as important mechanisms of FEN-induced cardiotoxicity in zebrafish. Overall, this study delineated the key mechanisms of FEN-triggered cardiotoxicity and identified RES as a promising candidate for therapeutic intervention.