Resveratrol Attenuates Sepsis-Induced Cardiomyopathy in Rats through Anti-Ferroptosis via the Sirt1/Nrf2 Pathway. Issue 1 (31st December 2023)

• Record Type: Journal Article
• Authors: Zeng, Youcheng; Cao, Guodong; Lin, Liang; Zhang, Yixin; Luo, Xiqing; Ma, Xiaoyu; Aiyisake, Akelibieke; Cheng, Qinghong
• Is Part Of: Journal of investigative surgery. Volume 36:Issue 1(2023)
• Publication Date: 2023-12-31
• Subjects: sepsis-induced cardiomyopathy -- resveratrol -- ferroptosis -- CLP -- Sirt1/Nrf2; Surgery -- Research -- Periodicals; Research; Surgery; Surgical Procedures, Operative; 617.075
• DOI: 10.1080/08941939.2022.2157521
• Languages: English
• ISSNs: 0894-1939

Abstract

Abstract: Background: Sepsis-induced cardiomyopathy (SIC) is a severe myocardial dysfunction secondary to septicemia. It is a major concern owing to the high mortality and morbidity, which are greatly influenced by ferroptosis. Resveratrol (RSV) is a naturally existing agonist of the silent information regulator 1 (Sirt1). It has cardioprotective effects against sepsis-induced myocardial injury, However, the detailed mechanism is unknown. Methods: In this study, cecal ligation and puncture (CLP)-induced septic rats were employed to assess the changes in ferroptosis with RSV administration. According to the different treatments the rats were divided into the following groups: (1) the Sham, (2) CLP, (3) CLP + RSV at various doses (10, 30, and 50 mg/kg), and (4) CLP + Fer-1(a ferroptotic inhibitor) groups. After 24 h, the structure and function of the cardiac system in rats were evaluated, and mitochondrial morphology, ferroptosis-related biomarkers, and the levels of Sirt1/Nrf2 were assessed. Results: The rats that underwent CLP had suffered cardiac dysfunction, accompanied with myocardial damage, impaired mitochondria, elevated lipid peroxidation, and reduced Sirt1/Nrf2 expression in the myocardium. High-dose RSV successfully improved heart function, reversing the abnormalities in a dose-dependent manner. We then used EX527, a selective Sirt1 inhibitor, to further identify the intermediate signaling targets of RSV that regulate ferroptosis. EX527 diminished the curative effects of high-doses RSV. Conclusions: Summarily, our findings suggest a novel mechanism of RSV in reducing SIC: ferroptosis inhibition via upregulation of Sirt1/Nrf2 signaling pathways. This may be an effective therapeutic approach against organ failure in sepsis, particularly SIC.