A comparative study of the cardioprotective effect of Metformin, Sitagliptin and Dapagliflozin on Isoprenaline induced myocardial infarction in non-diabetic rats

Abstract

Background Acute myocardial infraction (AMI) is a leading cause of morbidity. As anti-diabetic drugs affect the cardiovascular risk of diabetic patients independent of their glucose lowering effect, this study was aimed to explore the cardioprotective effects of metformin, sitagliptin and dapagliflozin on electrocardiogram (ECG) changes, IL-1β, troponin I, caspase 3 in isoprenaline (ISO) induced MI in non-diabetic rats. The present study was conducted on 40 adult male Wistar albino rats. The rats were randomly assigned into 5 groups, 8 each: I-Normal Control (NC) group, II-ISO-induced MI control (ISO-MI) injected with ISO subcutaneously at a dose of 100 mg/kg to induce experimental AMI. III-A- Metformin treated ISO-induced MI group (300 mg/kg/day), III-B-Sitagliptin treated ISO-induced MI group (10 mg/kg/day) and III-C- Dapagliflozin treated ISO-induced MI group (5 mg/kg/day). Results Treated groups showed significant improvement at p < 0.05 of ECG parameters with a decrease HR, ST amplitude and QT interval as compared to ISO-MI group. There was significant reduction at p < 0.05 of serum levels of IL-1β, troponin I and caspase 3 in the treated groups. Conclusions All medications proved to be effective in alleviating the harmful effects caused by ISO-induced MI evidenced by ECG readings and biochemical parameters. However, Dapagliflozin demonstrated a superior effect to Metformin and Sitagliptin.

Metformin and Carvedilol Ameliorate Isoprenaline-Induced Myocardial Infarction in Non-Diabetic Rats Through Ampk Activation and Suppression of Apoptosis

“…In the present study, the elevated levels of serum cardiac injury cTn-I and LDH after ISO administration indicated a significant impairment of myocardial function. Our results are in harmony with the prior reports [29][30][31] . Cardiomyocyte damage in ISOinduced MI is caused by an excess of ROS and cytotoxic free radicals, which disrupted the integrity and function of myocardial membranes and released intracellular cardiac enzymes like the cTn-I 32 .…”

“…Our results showed a significant increase in caspase-3 level in the ISO-treated group. This is in accordance with Ibrahim et al, 31 and Hasan et al, 39 results indicating enhanced apoptosis of cardiomyocytes. Increased ROS, followed by lipid peroxidation in heart tissue and immediate DNA damage, could account for this.…”

Different Mechanisms in Doxorubicin-Induced Cardiomyopathy: Impact of BRCA1 and BRCA2 Mutations

“…Acute DIC is reversible and often manifests with tachycardia and ventricular premature beats shortly following administration. Histological features of acute DIC in the myocardium include interruption of myofibrils, cytoplasmic vacuolation, and sparsity in cardiomyocytes [11]. The incidence of chronic DIC is ~2-20% and typically manifests as a complication of breaching Dox dosage tolerance after weeks or months of administration, featuring irreversible cardiomyopathy, prominent left ventricular enlargement, and heart failure [10,12,13].…”