Document Type : Original Article
Authors
1
Department of Clinical pharmacology, Faculty of Medicine, Sohag University
2
Department 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
)
View on SCiNiTO