Rosuvastatin and ellagic acid protect against isoproterenol-induced myocardial infarction in hyperlipidemic rats

Abstract

Hyperlipidemia (HL) with subsequent coronary atherosclerosis is the major trigger of ischemia and hence, myocardial infarction (MI) occurs. The present study aimed to elucidate the effects of pretreatment with rosuvastatin and ellagic acid, as well as their combination on isoproterenol-induced MI in hyperlipidemic rats. Adult rats were fed with a cholesterol-rich diet for seven weeks and received rosuvastatin (10 mg/kg) and/or ellagic acid (30 mg/kg) by oral gavage daily starting from the fifth week then subcutaneously injected with two doses 24-h apart of 100 mg/kg isoproterenol in the last two days. ECG pattern was monitored and both cardiac biomarkers (cTnI, CK-MB, LDH and AST) and lipid profile (TC, TG, HDL-c and LDL-c) were measured in serum. MDA and GSH levels were quantified in cardiac homogenates and heart tissue damage was examined by histopathology. Furthermore, the expression levels of iNOS, eNOS, Bax and Bcl-2 in heart samples were assessed by western blotting. Three-week pretreatment with rosuvastatin and/or ellagic acid markedly ameliorated HL- and isoproterenol-induced alterations in ECG, cardiac markers, oxidation markers, lipid profile and heart architecture. Both drugs downregulated iNOS and upregulated eNOS, while only rosuvastatin and the combination downregulated Bax. This study provides evidence that rosuvastatin and ellagic acid possess cardioprotective effect on the hyperlipidemic-myocardial infarction rat model and the combination does not offer extra protection than monotherapy.

Keywords

• Myocardial infarction
• Hyperlipidemia
• Isoproterenol
• Rosuvastatin
• Ellagic acid