Etomidate ameliorates ferroptosis and mitochondrial damage in myocardial ischemia/reperfusion injury.

Abstract

Etomidate plays a protective role in ischemia/reperfusion diseases. The aim of this study was to investigate its mechanism in ameliorating myocardial ischemia/reperfusion injury (MI/RI). Experimental models of MI/RI in rats and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes were established to examine the myocardial protective properties of Etomidate. The effects of Etomidate on myocardial tissue damage were evaluated by echocardiography, serum cardiac enzymes, myocardial hematoxylin and eosin (H&E) staining and Masson staining. Cardiomyocyte injury was determined by detecting cell viability and the levels of lactate dehydrogenase. Mitochondrial function of cardiomyocytes was assessed by mitochondrial membrane potential, adenosine triphosphate (ATP) content, and mitochondrial reactive oxygen species (ROS). Iron content, oxidative- and ferroptosis-related biomarkers were measured. Ferroptosis inducer Erastin was utilized for mechanistic investigation. In results Etomidate alleviated ischemia/reperfusion-induced myocardial injury, ferroptosis and mitochondrial injury in rats in a dose-dependent pattern. Etomidate also increased cell viability, attenuated mitochondrial damage, and reduced intracellular iron and lipid peroxidation in cardiomyocytes with hypoxia-reoxygenation (H/R) injury. Moreover, the protective effects of Etomidate against MI/RI or H/R injury were abolished by Erastin intervention. Our study elucidated the correlation between Etomidate and ferroptosis and mitochondrial damage following MI/RI, concluding that Etomidate may exert a protective effect against MI/RI by mitigating ferroptosis and mitochondrial damage. This discovery provides novel insights into the pharmacological mechanisms of Etomidate in the context of MI/RI.