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.