College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
College of Animal Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
J Agric Food Chem. 2022 Dec 21;70(50):15962-15971. doi: 10.1021/acs.jafc.2c07484. Epub 2022 Dec 2.
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.
氟广泛应用于农业生产和食品包装中。水中和食物中过量的氟化物对肝脏健康构成严重威胁。α-硫辛酸是一种天然的自由基清除剂，具有护肝作用。然而，α-硫辛酸对氟肝毒性的保护作用尚不确定。本研究旨在探讨α-硫辛酸预防氟中毒性肝损伤的铁死亡机制。将 5 周龄 ICR 小鼠用氟化钠（100mg/L）和/或 α-硫辛酸（200mg/kg）处理 9 周。结果表明，α-硫辛酸减轻了氟化物引起的肝形态和超微结构损伤。此外，α-硫辛酸减轻了氟化物引起的肝内铁蓄积、氧化应激和脂质过氧化。此外，机制研究发现，α-硫辛酸通过 System Xc/GPX4 轴、脂质过氧化轴和铁代谢轴来预防氟化物诱导的铁死亡，但有趣的是，它在肝细胞中不受线粒体自由基轴的调节。总之，本研究表明，α-硫辛酸通过抑制铁死亡来预防氟化物引起的肝损伤，这对于预防和治疗氟化物引起的肝损伤具有潜在意义。
