Abstract
Isoproterenol (ISO) induces myocardial injuries in the form of ischemia and infarction (MI). Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-metliyiglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to evaluate the effect of pretreatment with SIM on ISO-induced cardiac infarction in rats. Forty-eight rats were divided into four groups. Group I (control) received normal saline.; Group II (SIM) received SIM (10 mg/kg body weight, orally by gavage) for 30 days. Group III (ISO) received ISO (5 mg/kg) intraperitoneally for 7 days to induce cardiac injury. Group IV (ISO/SIM); received SIM (10 mg/kg body weight, orally by gavage) for 30 days and in the last 7 days they received ISO (5 mg/kg) intraperitoneally. Serological analysis for detection of cardiac injury markers (troponin-T and creative phosphokinase-MB "CPK-MB") and inflammatory markers (IL-6 and TNF-alpha) was done. Cardiac tissues were processed for histological examination (H&E and Masson's trichrome) and for the immunohistological quantitative analysis of CD68. Administration of ISO induced an increase in heart weight to body weight (HW/BW) ratio and elevation of systolic and diastolic blood pressure. Serological analysis revealed an increase of interleukin-6, troponin-T, (CPK-MB), and tumor necrosis factor-alpha (TNF-alpha). Histopathological examination of heart tissue revealed thickening of the left ventricle and inter-ventricular septum, large focal areas of sub-endocardial degeneration, mononuclear cellular infiltrations, and massive interstitial fibrosis. In addition, ISO-treated rats exhibited significant up-regulation of CD68. Pre-treatment with SIM significantly attenuated ISO-induced cardiac hypertrophy and necrosis, alleviated the elevated biochemical parameters and CD68 expression, and improved the heart histopathological changes. This study provides evidence that SIM minimizes the ischemic effect of ISO on the heart of rats through inhibition of inflammatory cellular infiltration, especially macrophages, as confirmed by down-regulation of CD68. (C) 2016 The Authors. Published by IASE.