Lu Yuzhen, Hu Junjie, Chen Liang, Li Shan, Yuan Ming, Tian Xianxiang, Cao Peng, Qiu Zhenpeng
College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China.
Front Pharmacol. 2023 May 15;14:1196287. doi: 10.3389/fphar.2023.1196287. eCollection 2023.
Ferroptosis is an iron-dependently nonapoptotic cell death characterized by excessive accumulation of lipid peroxides and cellular iron metabolism disturbances. Impaired iron homeostasis and dysregulation of metabolic pathways are contributors to ferroptosis. As a major metabolic hub, the liver synthesizes and transports plasma proteins and endogenous fatty acids. Also, it acts as the primary location of iron storage for hepcidin generation and secretion. To date, although the intricate correlation between ferroptosis and liver disorders needs to be better defined, there is no doubt that ferroptosis participates in the pathogenesis of liver diseases. Accordingly, pharmacological induction and inhibition of ferroptosis show significant potential for the treatment of hepatic disorders involved in lipid peroxidation. In this review, we outline the prominent features, molecular mechanisms, and modulatory networks of ferroptosis and its physiopathologic functions in the progression of liver diseases. Further, this review summarizes the underlying mechanisms by which ferroptosis inducers and inhibitors ameliorate liver diseases. It is noteworthy that natural active ingredients show efficacy in preclinical liver disease models by regulating ferroptosis. Finally, we analyze crucial concepts and urgent issues concerning ferroptosis as a novel therapeutic target in the diagnosis and therapy of liver diseases.
铁死亡是一种铁依赖性非凋亡性细胞死亡，其特征是脂质过氧化物过度积累和细胞铁代谢紊乱。铁稳态受损和代谢途径失调是铁死亡的促成因素。作为主要的代谢枢纽，肝脏合成并运输血浆蛋白和内源性脂肪酸。此外，它还是铁储存的主要场所，用于铁调素的生成和分泌。迄今为止，尽管铁死亡与肝脏疾病之间的复杂关系尚需进一步明确，但毫无疑问，铁死亡参与了肝脏疾病的发病机制。因此，铁死亡的药理学诱导和抑制在治疗脂质过氧化相关肝脏疾病方面显示出巨大潜力。在本综述中，我们概述了铁死亡的显著特征、分子机制、调节网络及其在肝脏疾病进展中的生理病理功能。此外，本综述总结了铁死亡诱导剂和抑制剂改善肝脏疾病的潜在机制。值得注意的是，天然活性成分通过调节铁死亡在临床前肝脏疾病模型中显示出疗效。最后，我们分析了将铁死亡作为肝脏疾病诊断和治疗新靶点的关键概念和紧迫问题。
