Protective effects of resveratrol against perfluorooctane sulfonamide-induced cardiac developmental toxicity in zebrafish larvae.

We have reported that Perfluorooctane sulfonamide (PFOSA), a direct precursor of perfluorooctane sulfonic acid (PFOS), disrupts cardiac development by activating the aryl hydrocarbon receptor (AhR) and inducing oxidative stress. Resveratrol (RSV) is a natural polyphenolic compound with both AhR-inhibitory and antioxidant properties. Therefore, we hypothesized that RSV may exert protective effects against PFOSA-induced cardiac defects. In the present study, we demonstrated that PFOSA exposure led to cardiac malformations and functional impairments in zebrafish embryos, effects that were significantly alleviated by RSV. Mechanistically, RSV not only suppressed PFOSA-induced oxidative stress, reduced reactive oxygen species (ROS) levels, normalized gstp1, cat, sod2 expression, but attenuated AhR activation (downregulation of cyp1a1 and nqo1). Additionally, RSV mitigated PFOSA-induced endoplasmic reticulum stress, reduced C/EBP homologous protein (Chop) expression and eIF2α phosphorylation, alleviated mitochondrial damage (lowered mitochondrial ROS, restored membrane potential), and suppressed apoptosis (fewer apoptotic bodies, decreased cleaved caspase-3). Collectively, these findings indicate that RSV protects against PFOSA-induced cardiac defects by inhibiting PFOSA-induced AhR activation and oxidative stress, thereby suppressing downstream ER stress, mitochondrial damage, and apoptosis processes.