METFORMIN AND CARVEDILOL AMELIORATE ISOPRENALINE-INDUCED MYOCARDIAL INFARCTION IN NON-DIABETIC RATS THROUGH AMPK ACTIVATION AND SUPPRESSION OF APOPTOSIS | ||||
| Bulletin of Pharmaceutical Sciences Assiut University | ||||
| Volume 46, Issue 2, December 2023, Page 1377-1395 PDF (1.61 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/bfsa.2023.327645 | ||||
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| Authors | ||||
Eman Mohammed Ali  1; Azza MA. Abouelella2
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| 1Department of Clinical pharmacology, Faculty of Medicine, Sohag University | ||||
| 2Department of Clinical Pharmacology, Faculty of Medicine, Sohag University, Egypt | ||||
| Abstract | ||||
| The objective of this study was to clarify the ameliorative effect of metformin (MET), carvedilol (CAR), and their combination and the underlying mechanisms in a non-diabetic rat model of isoprenaline (ISO)-induced MI. The adult male Wistar rats were allocated into six groups (n=8). Control group A received saline while control group B received DMSO 0.5% (i.p) for 10 days. ISO-treated group: received ISO (85 mg/kg.i.p.) on the first and second day of the experiment with the injection of normal saline for 10 days from the first day. ISO+MET and ISO+CAR-treated groups: received ISO as previously described and MET (200 mg/kg.i.p.) and CAR (10 mg/kg.i.p.) respectively for 10 days from the first day of the experiment. ISO+MET+CAR-treated group: received ISO, MET, and CAR as previously described. In the ISO group, the rise in serum cardiac biomarkers cTn-I and LDH provided evidence of MI. In addition, cardiac MDA, IL6, caspase-3, and Bax gene levels were significantly elevated, while cardiac SOD, GSH, pAMPK, eNOS, Bcl-2 gene, and Bcl-2/Bax ratio levels were significantly reduced with histopathological changes in cardiac tissue. Whereas posttreatment with MET, CAR, and their combination significantly reversed these overwhelming ISO-induced damaging effects on the heart. In conclusion, MET, CAR, and their combination could improve myocardial injury in ISO-induced MI through AMPK signaling pathway activation, and anti-apoptotic, anti-inflammatory, and antioxidant mechanisms. Subsequently, promote the recovery of cardiomyocyte function. | ||||
| Keywords | ||||
| Metformin; Carvedilol; Myocardial infarction; AMPK; Apoptosis; Gene expression | ||||
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