Effect of GLP-1 Receptor Agonist on Ischemia Reperfusion Injury in Rats with Metabolic Syndrome

Abstract

Metabolic syndrome (MetS) represents an important factor that increases the risk of myocardial infarction, and more severe complications. Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs) exhibit cardioprotective potential, but their efficacy in MetS-related myocardial dysfunction has not been fully explored. Therefore, we aimed to assess the effects of exenatide and dulaglutide on heart function and redox balance in MetS-induced rats. Twenty-four Wistar albino rats with induced MetS were divided into three groups: MetS, exenatide-treated (5 µg/kg), dulaglutide-treated (0.6 mg/kg). After 6 weeks of treatment, in vivo heart function was assessed via echocardiography, while ex vivo function was evaluated using a Langendorff apparatus to simulate ischemia-reperfusion injury. Heart tissue samples were analyzed histologically, and oxidative stress biomarkers were measured spectrophotometrically from the coronary venous effluent. Both exenatide and dulaglutide significantly improved the ejection fraction by 3% and 7%, respectively, compared to the MetS group. Histological analyses corroborated these findings, revealing a reduction in the cross-sectional area of cardiomyocytes by 11% in the exenatide and 18% in the dulaglutide group, indicating reduced myocardial damage in GLP-1RA-treated rats. Our findings suggest strong cardioprotective potential of GLP-1RAs in MetS, with dulaglutide showing a slight advantage. Thus, both exenatide and dulaglutide are potentially promising targets for cardioprotection and reducing mortality in MetS patients.

Keywords

• metabolic syndrome
• GLP-1 agonists
• oxidative stress
• cardioprotection