Student Research Committee, 37552Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmacodynamics and Toxicology, School of Pharmacy, 37552Mashhad University of Medical Sciences, Mashhad, Iran.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S851-S860. doi: 10.1177/09603271211052987. Epub 2021 Nov 8.
Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities.
铁死亡是一种铁依赖性的程序性细胞死亡形式，其特征为铁过载、活性氧（ROS）生成增加、谷胱甘肽（GSH）耗竭和脂质过氧化。亲脂性抗氧化剂和铁螯合剂可以预防铁死亡。GSH 依赖性谷胱甘肽过氧化物酶 4（GPX4）可以防止脂质 ROS 积累。铁死亡被认为是通过 GPX4 失活而引发的。此外，铁蛋白降解导致的线粒体铁过载参与了 ROS 生成的增加。铁死亡被认为可以解释几种药物和化学物质引起的器官毒性的作用机制。抑制铁死亡可能为治疗甚至预防这种器官毒性提供新的治疗机会。
