EVALUATION OF SIMVASTATIN EFFECT ON ISOPROTERENOL INDUCED MYOCARDIAL INJURY IN RATS THROUGH DOWN-REGULATION OF NF-κB, BAX AND Bcl-2. Raeesa Abdel-Tawab Mohamed Department of Anatomy, College of Medicine, King Saud University, Saudi Arabia. Department of Histology, College of Medicine, Cairo University, Egypt.
Background: Light microscopy and serological analysis are most widely used to evaluate the morphological and serological changes that have acquired in myocardial injury. Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. Objective: The present study was designed to evaluate the effect of pre-treatment with SIM on isoproterenol (ISP)-induced cardiac injury (hypertrophy and ischemia) in rats. Material and Methods: Twenty-eight rats weighing 230±20 g were divided into four groups. Group I (Control); received normal saline. Group II (Control SIM); received SIM (10 mg/kg body weight-orally by gavage) for 30 days. Group III (ISP); administered ISP (5 mg/kg) intra-peritoneal for 7 days to induce cardiac injury. Group IV (ISP+SIM); received SIM (10 mg/kg body weight-orally by gavage) for 30 days and in the last 7 days they were administered ISP (5 mg/kg) intra-peritoneal. Serological analysis for detection of cardiac injury markers (troponin-T and creatine phosphokinase-MB “CPK-MB”) and inflammatory markers (IL-6 and TNF-α) was done. Cardiac tissues were processed for histological and immune-histological analysis for determination of NF-κB, Bax and Bcl-2 Results: Administration of ISP induced an increase in heart-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 tumour necrosis factor- α (TNF-α). Histopathological examination of heart tissue revealed thickening of the left ventricle and inter-ventricular septum, focal areas of sub-endocardium degeneration, mononuclear cellular infiltrations and massive interstitial fibrosis. In addition ISP-administered rats exhibited significant up-regulation of nuclear factor-kappa B (NF-κB), anti-apoptotic (Bcl-2), and pro-apoptotic (Bax) proteins. Pre-treatment with SIM significantly attenuated ISP-induced cardiac hypertrophy, necrosis, and alleviated the elevated biochemical parameters, and improved the heart histological architecture. Conclusion: This study provides evidence that SIM prevented the development of cardiac injury and apoptosis via modulation of the pro and –apoptotic transducer and activator of transcription-signalling pathway in the heart of ISP-administered animals.