α-Lipoic Acid Alleviated Fluoride-Induced Hepatocyte Injury via Inhibiting Ferroptosis
Yangfei Zhao, Xueyan Liu, Chen Liang, Ting Pei, Mingyue Guo, Jundong Wang, Jianhai Zhang
Abstract
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.