Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China; Jinan Vocational College of Nursing, Jinan, Shandong, PR China.
Toxicol In Vitro. 2022 Aug;82:105388. doi: 10.1016/j.tiv.2022.105388. Epub 2022 May 18.
Alcoholic liver disease has become one of the main causes of liver injury, and its prevention and cure are important medical tasks. Silibinin, a natural flavonoid glycoside, is a conventional hepatic protectant. This study elucidates the modulation of ferroptosis in silibinin's protective effects on ethanol- or acetaldehyde-induced liver cell damage by using human carcinomatous liver HepG2 cells and immortalized liver HL7702 cells. Our results show that ferroptosis is induced in the cells treated with ethanol or acetaldehyde, as evidenced by the increased ROS stress and iron level. Silibinin resolves the oxidative stress and reduces iron level. Ferroptosis induced by ethanol- or acetaldehyde involving nuclear receptor co-activator 4 (NCOA4)-dependent autophagic degradation of ferritin, a protein for storing iron is rescued by silibinin. PINK1 and Parkin-mediated mitophagy is arrested in ethanol- or acetaldehyde-treated cells but reversed by silibinin. Ferritin degradation and ROS level are further increased when PINK1 or Parkin is silenced in the cells treated with ethanol or acetaldehyde. Collectively, our study reveals that silibinin inhibits ethanol- or acetaldehyde-induced ferroptosis in two liver cell lines, HepG2 and HL7702 cells, providing new therapeutic strategies for alcoholic liver injury.
酒精性肝病已成为肝损伤的主要原因之一，其防治是重要的医学任务。水飞蓟宾是一种天然黄酮类化合物，是一种常规的肝保护剂。本研究通过人肝癌 HepG2 细胞和永生化肝 HL7702 细胞，阐明了水飞蓟宾在保护乙醇或乙醛诱导的肝细胞损伤中的铁死亡调节作用。我们的结果表明，乙醇或乙醛处理的细胞中诱导了铁死亡，这可通过增加 ROS 应激和铁水平来证明。水飞蓟宾可解决氧化应激并降低铁水平。水飞蓟宾可挽救乙醇或乙醛诱导的涉及核受体共激活因子 4（NCOA4）依赖性铁蛋白自噬降解的铁死亡，铁蛋白是储存铁的蛋白质。PINK1 和 Parkin 介导的线粒体自噬在乙醇或乙醛处理的细胞中被阻断，但可被水飞蓟宾逆转。当在乙醇或乙醛处理的细胞中沉默 PINK1 或 Parkin 时，铁蛋白降解和 ROS 水平进一步增加。综上所述，本研究揭示了水飞蓟宾抑制两种肝细胞系 HepG2 和 HL7702 中的乙醇或乙醛诱导的铁死亡，为酒精性肝损伤提供了新的治疗策略。
