Anti-inflammatory, Anti-oxidative and Athero-protective effects of Irbesartan in rabbits with Atherogenic diet

Abstract

Abstract: The disorder of atherosclerosis is a dysfunction of endothelium due to inflammation of the blood vessel wall. In primary phases it characterized by activation and recruitment of macrophages. Irbesartan, an angiotensin receptor blocker, has ability to activate a peroxisome proliferator-activated receptor gamma. Numerous studies have been showed that management with angiotensin II blockers (ARBs) can alleviate formation of atherosclerotic plaque, however the underlining mechanism still obscure. Objectives: The present study is to evaluate the athero-protective actions of irbesartanvia reduction of inflammation and oxidative stress. Methods: This study enrolled twenty four male rabbits which were arbitrarily separated into 3 groups (every group contain 8 rabbits). All groups were fed for 12 weeks with normal chow (oxiod) diet (group I), normal chow (oxiod) diet with 0.05 % high cholesterol diet (Group II) and normal chow (oxiod) diet with 0.05 % high cholesterol diet together with 0.5 mg/kg irbesartanonce daily atmorning) (Group III). Samples of blood were analyzed at (time zero) and every 4 weeks of study to assess serum endothelin-1 (ED-1), intracellular adhesion molecule-1 (ICAM-1) and HDL-Cholesterol, triglycerides (TG), total cholesterol (TC). At the end the study (12 weeks) the aorta was collected to evaluate the aortic intimal thickness and the levels of aortic reduced glutathione (GSH) and aortic malondialdehyde (MDA). Results: Irbesartan treated group revealed in significant change of lipid parameters of when evaluate with group II (P > 0.05). However Irbesartan significantly decreased the elevated endothelin-1, Intracellular adhesion molecule-1, aortic intimal thickness and aortic MDA and restored aortic GSH level when compare with group II (P < 0.05). Conclusions: Irbesartan could participate in reduction of atherosclerosis progression in rabbit fed with rich cholesterol diet by interfering with inflammatory and oxidative pathways.