Apigenin Alleviates Fumonisin B1-Induced Hepatotoxicity by Suppressing Ferroptosis through the Nrf2/FSP1 Pathway.

Fumonisin B1 (FB1) is a common mycotoxin known to cause hepatotoxicity in various species. However, whether ferroptosis is involved in its toxicity remains unclear, and effective interventions are lacking. Apigenin (AG) is a natural antioxidant with recognized cytoprotective properties. In this study, we investigated ferroptosis in FB1-induced liver injury and explored AG's protective effects via the Nrf2/FSP1 pathway. FB1 triggered ferroptosis in hepatocytes, evidenced by decreased ubiquinol (CoQ10H2), Nrf2, and ferroptosis suppressor protein 1 (FSP1) levels, and increased Fe2+ levels, NAD+/NADH ratio, and lipid peroxidation (LPO). Both ferrostatin-1 and AG attenuated FB1-induced ferroptosis by upregulating CoQ10H2 and suppressing LPO, with effects similar to those of Nrf2 or FSP1 overexpression. However, knockdown of either Nrf2 or FSP1 abolished AG's protective effects against FB1-induced ferroptosis. Collectively, this study reveals a novel mechanism by which AG activates the Nrf2/FSP1 pathway to counteract FB1-induced hepatotoxicity, suggesting its potential as a hepatoprotective agent against environmental toxins.