Nomilin mitigates OBS-induced developmental cardiotoxicity via the Nrf2 pathway

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is widely used in industry as a replacement for perfluorooctanesulfonic acid (PFOS) and has attracted considerable attention due to its environmental persistence and toxicity. However, limited information is available regarding its effects and underlying mechanisms in aquatic organisms, particularly its cardiotoxic potential. In the current study, zebrafish (Danio rerio) embryos were selected to elucidate the developmental and cardiac toxicity of OBS, as well as the potential protective role of the citrus limonoid nomilin (NOM). Embryos exposed to 0.1 and 1 mg/L OBS for 96 h exhibited marked developmental and cardiac abnormalities, including reduced body length, abnormal hatching and survival rates, pericardial edema, and decreased heart rate. OBS exposure also dysregulated the expression of key cardiac development genes (vmhc, gata4, nkx2.5, and sox9b), and significantly decreased the transcript levels of oxidative stress (OS)-related genes (keap1, nrf2, and ho-1), indicating OS induction. Activation of Nrf2 signaling by NOM treatment significantly attenuated OBS-induced cardiotoxic effects. These findings demonstrate that prenatal OBS exposure can cause cardiac oxidative injury and developmental defects via the Keap1/Nrf2 pathway.