α-Lipoic Acid Alleviated Fluoride-Induced Hepatocyte Injury via Inhibiting Ferroptosis

Fluoride is widely used in agricultural production and food packaging. Excessive fluoride in water and food is a serious threat to liver health. α-Lipoic acid, a natural free radical scavenger, has hepatoprotective properties. However, the protective effect of α-lipoic acid on fluorohepatotoxicity is uncertain. The aim of this study was to investigate the mechanism of ferroptosis in α-lipoic acid preventing fluoride-induced hepatotoxicity. Five-week-old ICR mice were treated with sodium fluoride (100 mg/L) and/or α-lipoic acid (200 mg/kg) for 9 weeks. The results showed that α-lipoic acid attenuated fluoride-induced damage to liver morphology and ultrastructure. Moreover, α-lipoic acid alleviated fluoride-induced iron accumulation, increased oxidative stress, and elevated lipid peroxidation in the liver. In addition, the mechanism study found that α-lipoic acid prevented fluoride-induced ferroptosis through the System Xc^-/GPX4 axis, lipid peroxidation axis, and iron metabolism axis, but it was interestingly not regulated by mitochondrial free radical axis in the hepatocytes. Altogether, this study indicated that α-lipoic acid prevents fluoride-induced liver injury by inhibiting ferroptosis, which has potential implications for the prevention and treatment of fluoride-induced liver injury.