Effect of GLP-1 Receptor Agonist on Ischemia Reperfusion Injury in Rats with Metabolic Syndrome.
Marko RavicIvan M SrejovicJovana N JeremićMarijana AndjicJasmina Z SretenovicMaja MuricMarina R NikolicSergey BolevichKirill Alekseevich KasabovVladimir Petrovich FisenkoAleksandra Z StojanovicJakovljevic Lj VladimirPublished in: Pharmaceuticals (Basel, Switzerland) (2024)
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.
Keyphrases
- ejection fraction
- oxidative stress
- metabolic syndrome
- left ventricular
- diabetic rats
- aortic stenosis
- ischemia reperfusion injury
- heart failure
- newly diagnosed
- cross sectional
- high glucose
- coronary artery disease
- coronary artery
- atrial fibrillation
- rheumatoid arthritis
- insulin resistance
- drug induced
- dna damage
- uric acid
- wastewater treatment
- cardiovascular events
- early onset
- risk assessment
- cardiovascular risk factors
- aortic valve
- transcatheter aortic valve replacement
- heat shock protein
- stress induced
- heat shock
- endoplasmic reticulum stress