Evaluation of the Effects of Glimepiride (Amaryl) 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, staffing and activation of monocyte/ macrophages. Glimepiride is one of the third generation sulphonylurea drugs useful for manage of diabetes mellitus type tow and it may exert anti inflammatory activity by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway.Objectives: The objective of the present study was to assess the effect of glimepiride on atherosclerosis via interfering with inflammatory and oxidative pathways.Methods: Eighteen local domestic male rabbits were involved in this study. The animals were randomly divided into three 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 ). Blood samples were collected before (0 time) and every two weeks on 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 (MDA), (GSH) and aortic intimal thickness. Results: Glimepiride treatment don’t show significant effect on lipid parameters compared with induced untreated group (P > 0.05). Glimepiride significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P<0.05).Also it restore aortic GSH level (P <0.05). Conclusions: Glimepiride may reduce atherosclerosis progression in hypercholesterolemic rabbit via interfering with inflammatory and oxidative pathways without affecting lipid parameters.