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Published on: May 26, 2022
Eplerenone attenuates cardiac dysfunction and oxidative stress in β-receptor stimulated myocardial infarcted rats
Navya M Reddy1, Umesh B Mahajan1, Chandragouda R Patil1
1Cardiovascular Pharmacology Division, Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research Shirpur-Dist-Dhule, Maharashtra, India.
Abstract:
Eplerenone is a competitive antagonist of the aldosterone receptor with an additional PI3K-Akt activity. The existing cram has been intended to explore, whether eplerenone treatment attenuates the expansion of myocardial infarction in isoproterenol treated rats by restoring hemodynamic, biochemical, and histopathological changes. Isoproterenol induced cardiotoxicity was evidenced by marked ST elevation, decrease in systolic, diastolic, mean arterial pressures. Maximal positive rate of developed left ventricular pressure (+LVdP/dt max, a indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dt max, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load) were also shown. In addition, a significant reduction in activities of myocardial creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione level along with increase in malondialdehyde content were observed. Oral pre-treatment with eplerenone (50, 100 and 150 mg/kg) daily for a period of 14 days, constructively modulated the studied parameters in isoproterenol-induced myocardial injury. The protective role of eplerenone on isoproterenolinduced myocardial damage was further confirmed by histopathological examinations. Eplerenone at doses of 100 mg/kg and 150 mg/kg produced more pronounced protective effects than 50 mg/kg body weight. Together, our study provides evidence for protective effects of eplerenone on myocardium in experimentally induced myocardial infarction.
Insights
Eplerenone treatment protected against isoproterenol-induced myocardial infarction in rats. It improved heart function and reduced cardiac damage by restoring hemodynamic, biochemical, and histopathological changes.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Myocardial infarction (MI) involves significant cardiac damage.
- Isoproterenol is used to induce cardiotoxicity in experimental models.
- Eplerenone is an aldosterone receptor antagonist with PI3K-Akt activity.
Purpose of the Study:
- To investigate the protective effects of eplerenone against isoproterenol-induced myocardial infarction in rats.
- To evaluate eplerenone's impact on hemodynamic, biochemical, and histopathological parameters post-MI.
Main Methods:
- Rats were treated with isoproterenol to induce cardiotoxicity.
- Oral pre-treatment with eplerenone (50, 100, 150 mg/kg) was administered daily for 14 days.
- Hemodynamic, biochemical markers (cardiac enzymes, oxidative stress markers), and histopathological changes were assessed.
Main Results:
- Isoproterenol induced significant cardiotoxicity, evidenced by ECG changes, altered pressures, and reduced cardiac function.
- Eplerenone treatment dose-dependently restored hemodynamic parameters and cardiac enzyme activities.
- Eplerenone significantly reduced oxidative stress markers (malondialdehyde) and increased antioxidant levels (glutathione, catalase, SOD), confirmed by histopathology.
Conclusions:
- Eplerenone exhibits significant protective effects against experimental myocardial infarction.
- The cardioprotective mechanism involves restoring hemodynamic function and mitigating oxidative stress.
- Higher doses of eplerenone (100 and 150 mg/kg) demonstrated more pronounced protective effects.
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