Role of Ferroptosis Regulation by Nrf2/NQO1 Pathway in Alcohol-Induced Cardiotoxicity In Vitro and In Vivo
作者全名：Song, Chunpu; Li, Dongjie; Huang, Ling; Zhang, Jie; Zhao, Xiaoyan
作者地址：[Song, Chunpu; Li, Dongjie; Huang, Ling; Zhao, Xiaoyan] Southwest Univ, Coll Pharmaceut Sci, Chongqing 400716, Peoples R China; [Zhang, Jie] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400000, Peoples R China; [Zhao, Xiaoyan] Southwest Univ, Coll Pharmaceut Sci, Engn Res Ctr Coptis Dev & Utilizat, Minist Educ, Chongqing 400715, Peoples R China
通信作者：Zhao, XY (通讯作者)，Southwest Univ, Coll Pharmaceut Sci, Chongqing 400716, Peoples R China.; Zhang, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400000, Peoples R China.; Zhao, XY (通讯作者)，Southwest Univ, Coll Pharmaceut Sci, Engn Res Ctr Coptis Dev & Utilizat, Minist Educ, Chongqing 400715, Peoples R China.
来源：CHEMICAL RESEARCH IN TOXICOLOGY
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
WOS号：WOS:001239420900001
JCR分区：Q2
影响因子：3.7
年份：2024
卷号：37
期号：6
开始页：1044
结束页：1052
文献类型：Article
关键词：
摘要：The aim of the present study was to evaluate the cardiotoxic effects of alcohol and its potential toxic mechanism on ferroptosis in mice and H9c2 cells. Mice were intragastrically treated with three different concentrations of alcohol, 7, 14, and 28%, each day for 14 days. Body weight and electrocardiography (ECG) were recorded over the 14 day period. Serum creatine kinase (CK), lactic dehydrogenase (LDH), MDA, tissue iron, and GSH levels were measured. Cardiac tissues were examined histologically, and ferroptosis was assessed. In H9c2 cardiomyocytes, cell viability, reactive oxygen species (ROS), labile iron pool (LIP), and mitochondrial membrane potential (MMP) were measured. The proteins of ferroptosis were evaluated by the western blot technique in vivo and in vitro. The results showed that serum CK, LDH, MDA, and tissue iron levels significantly increased in the alcohol treatment group in a dose-dependent manner. The content of GSH decreased after alcohol treatment. ECG and histological examinations showed that alcohol impaired cardiac function and structure. In addition, the levels of ROS and LIP increased, and MMP levels decreased after alcohol treatment. Ferrostatin-1 (Fer-1) protected cells from lipid peroxidation. Western blotting analysis showed that alcohol downregulated the expression of Nrf2, NQO1, HO-1, and GPX4. The expressions of P53 and TfR were upregulated in vivo and in vitro. Fer-1 significantly alleviated alcohol-induced ferroptosis. In conclusion, the study showed that Nrf2/NQO1-dependent ferroptosis played a vital role in the cardiotoxicity induced by alcohol.
基金机构：Chongqing Research Program of Basic Research and Frontier Technology, China [cstc2021jcyj-msxmX0106]; Chinese Medicine Rehabilitation-the Key Discipline Constructed by Chongqing Health Bureau [2021-4322190044]
基金资助正文：The present study was supported by the Chongqing Research Program of Basic Research and Frontier Technology, China (grant no. cstc2021jcyj-msxmX0106) and Chinese Medicine Rehabilitation-the Key Discipline Constructed by Chongqing Health Bureau (grant no. 2021-4322190044).
