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

Authors :
Marko Ravic
Ivan Srejovic
Jovana Novakovic
Marijana Andjic
Jasmina Sretenovic
Maja Muric
Marina Nikolic
Sergey Bolevich
Kirill Alekseevich Kasabov
Vladimir Petrovich Fisenko
Aleksandra Stojanovic
Vladimir Jakovljevic
Source :
Pharmaceuticals, Vol 17, Iss 4, p 525 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

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.

Details

Language :
English
ISSN :
14248247
Volume :
17
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Pharmaceuticals
Publication Type :
Academic Journal
Accession number :
edsdoj.35f00667bcc4dcb944dc2e0e6173600
Document Type :
article
Full Text :
https://doi.org/10.3390/ph17040525