Gentisic acid protects Sprague-Dawley rats from myocardial infarction through reversing electrocardiographical, biochemical and histopathological abnormalities.

Abstract

Gentisic acid (GA), a cytochrome P450 metabolite of the antiplatelet drug aspirin, exhibits smooth muscle relaxant, antiatherogenic, and antioxidant activities. It also has a protective role in hypertrophic heart failure, suggesting its role in the management of myocardial infarction (MI). This study aimed to explore the protective activity of GA in isoproterenol (ISO)-induced MI in Sprague-Dawley (SD) rats in-vivo, followed by mechanistic investigation ex-vivo. SD rats were pretreated with different doses (5, 10, 15, and 20 mg/kg, i.p.) of GA for 21 days, followed by subcutaneous administration of ISO (85 mg/kg) on the 20th and 21st days. At the end of the experiment, electrocardiograph (ECG), blood pressure, myocardial injury marker enzymes, infarct size, lipid profile, and histological changes in myocardium were carried out. The possible underlying mechanisms were explored ex-vivo. GA prevented the ISO-induced changes in ECG parameters in rats in a dose-dependent manner. GA also reversed the fall in blood pressure associated with ISO treatment. GA diminished the elevated cardiac biomarkers and limited the infarcted area size (8 %) indicated by decrease in heart weight to body weight ratio. GA ameliorated the inflammation, edema, and necrosis and reduced collagen fiber deposition associated with ISO-induced MI. The results suggest that GA is an effective cardioprotective agent in rats by reversing ischemic changes in ECG and correcting histopathological and biochemical changes.