Abstract 135: Evaluation of the Effects of Glimepiride (Amaryl) and Repaglinide (Novonorm) on Atherosclerosis Progression in High Cholesterol-Fed Male Rabbits

Abstract

Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs useful for control of diabetes mellitus type two and it may exert anti inflammatory activity by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway . Repaglinide is a new hypoglycemic agent, a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has a favorable effect on the parameters of antioxidative balance. Objectives: The objective of present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with inflammatory and oxidative pathways. Methods: twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits fed with 1% cholesterol enriched diet. Group III rabbits fed with 1% cholesterol enriched diet together with Glimepiride (0.1mg/kg once daily before morning feed). Group IV rabbits fed with 1% cholesterol enriched diet together with Repaglinide (0.3mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), HDL-C, high sensitive C - reactive protein (hsCRP), IL-6 and TNF-α level. At the end of 10weeks the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Results: Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group ( P > 0.05).Also they were significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group ( P < 0.05),and they restore aortic GSH level ( P < 0.05) . Conclusions: Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbit via interfering with inflammatory and oxidative pathways without affecting lipid parameters.