Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase

Abstract

A B S T R A C TIschemic heart disease is a common cardiac health problem. Despite the significant advances in prevention and treatment of this disorder, its incidences and complications are very serious. So, the search for more antioxidants and anti-inflammatory agents with cardioprotective effects is an urgent task. We aimed to evaluate the effects of a heme oxygenase 1 (HO1) inducer, hemin (HEM), on isoprenaline (ISO)induced myocardial damage. Forty-five Wistar albino rats were used. Animals were treated with HEM (25 mg/kg/day) i.p. for 5 days and injected with ISO (150 mg/ kg/day) i.p. on 4th and 5th day of the experiment. Detection of the role of ATPsensitive potassium channel (K ATP ) was performed by administration of glibenclamide (GP) (5 mg/kg/day) orally 2 h before HEM. Moreover, the role of endothelial nitric oxide synthase (eNOS) was detected by coadministration of Nitro-x-L-arginine (L-NNA) (25 mg/kg/day) for 5 days. The ISO group showed increase in heart weight, cardiac enzymes, tumor necrosis factor alpha (TNFa), and malondialdehyde (MDA) with decrease in reduced glutathione (GSH), HO1, and total antioxidant capacity (TAC). In addition, there were increases in Bcl-2 associated X protein (Bax) and cleaved caspase-3, but decreases in B-cell lymphoma-2 (Bcl-2) and eNOS. Moreover, the histopathological examination of the ISO group showed degeneration of the cardiac muscle fibers and marked infiltration of the inflammatory cells. The biochemical and histopathological changes induced by ISO were markedly ameliorated in the HEM plus ISO group. This protective effect was diminished with coadministration of GP or L-NNA; thus, K ATP and eNOS might mediate HEM cardioprotection. I N T R O D U C T I O NCardiovascular diseases including myocardial infarction (MI) are among the most severe illnesses that could lead to death. MI occurs due to the imbalance between oxygen supply and oxygen demand followed by myocardial hypoxia [1]. This imbalance with the excessive release of reactive oxygen species (ROS) is a major contributing factor in the development of MI. Free radicals attack membrane lipids and mediate a chain of reactions of lipid peroxidation associated with disruption of the structure and permeability of cell membranes [2,3].Isoprenaline (ISO), a synthetic b-adrenergic agonist, causes severe oxidative stress and decreases oxygen supply in the myocardium leading to infarct-like necrosis in the heart muscles. The induction of MI using ISO is experimentally used to evaluate many cardiac ª 2019 Soci et e Franc ßaise de Pharmacologie et de Th erapeutique 302

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KATP channels are regulators of programmed cell death and targets for the creation of novel drugs against ischemia/reperfusion cardiac injury

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