Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis

• Published in: Gene 2022-01, Vol.808, p.145968-145968, Article 145968
• Main Authors: Li, Ting, Tan, Ying, Ouyang, Shao, He, Jin, Liu, Lingling
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Cell Line; Cell Survival - drug effects; Ferroptosis; Ferroptosis - drug effects; Ferroptosis - physiology; Glucose - metabolism; Heart - drug effects; Male; Myocardial ischemia-reperfusion; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Oxidative Stress - drug effects; Oxygen - metabolism; Protective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Resveratrol; Resveratrol - metabolism; Resveratrol - pharmacology; Signal Transduction - drug effects; Ubiquitination
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2021.145968

•Resveratrol protects against myocardial I/R injury.•Res protects against myocardial I/R injury via reducing oxidative stress and attenuating ferroptosis. Resveratrol (Res) is a polyphenol with a variety of biological activities. However, whether Res can prevent myocardial ischemia–reperfusion (I/R) injury is not yet known. This study aimed to investigate the protective effect of Res on myocardial I/R injury and to explore its potential mechanism. H9c2 cells were used for the in vitro experiments and oxygen-glucose deprivation/reoxygenation (OGD/R) model was established. Rats were ligated and perfused by the left anterior descending branch with or without Res (50 mg/kg·bw) for 14 days.The higher level of oxidative stress and Fe2+ content was observed in OGD/R-induced H9c2 cells than that of normal cells. OGD/R-induced H9c2 cells showed increased ferroptosis, mainly by reducing the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), but enhancing the expression of transferrin receptor 1 (TfR1). Both in vivo and in vitro experiments indicated that Res reduced the level of oxidative stress and Fe2 + content. In addition, Res inhibited ferroptosis, decreased TfR1 expression, and increased the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells and I/R rats. Moreover, we found that Res inhibited ferroptosis by the regulation of ubiquity specific peptidase 19 (USP19)-Beclin1 autophagy. Res protects against myocardial I/R injury via reducing oxidative stress and attenuating ferroptosis. Res could be a potential agent to the prevention of myocardial I/R injury.