Effect of vildagliptin on atherosclerosis progression in high cholesterol –fed male rabbits

Abstract

Back ground: Atherosclerosis is a disease of large and medium-sized muscular arteries and is a progressive disease characterized by the accumulation of lipids and fibrous elements in the large arteries.Objective: This study was undertaken to assess the effect of vildagliptin on atherosclerosis via interfering with inflammatory and oxidative pathwaysMaterials and Methods: 18 local domestic male rabbits were included in this study. The animals were randomly divided into three groups (6rabbits in each group): Group I rabbits fed normal chow (oxiod) diet for 12 weeks. Group II rabbits fed 1% cholesterol enriched diet for 12 weeks. Group III rabbits fed with cholesterol enriched diet for 6 weeks, and then continued on cholesterol enriched diet and treated with vildaglipin 50mg/kg/day orally for the next 6 weeks. Blood samples were collected at the start of the study, at 6weeks of the study and then at the end of treatment course to measure Serum lipids profile [(TC), (TG), (HDL)] , hsCRP and TNFα. At the end of the study the aorta were removed for measurement of aortic MDA ,glutathione, sectioning for histopathology and measuring aortic intima- media thicknessResults: Treatment of rabbits with vildagliptin for 6 weeks results in a significant reduction (P<0.05) in serum level of TC, TG, hsCRP and TNFα and a significant increase (P<0.05) in serum HDL level. There was a significant reduction (P<0.05) in aortic MDA and intima-media thickness, in comparison to the rabbits in the induced untreated control group. vildagliptin treatment cause significant increment (P<0.05) in aortic GSH in comparison to induced untreated group .Regarding histopathological results, vildagliptin treatment for 6 weeks results in a significant reduction (P<0.05) in atherosclerotic lesions in comparison to the induced untreated group and significant reduction in aortic intima- media thickness(P<0.05)Conclusions : vildagliptin reduced atherosclerosis progression in hyperlipidemic rabbit via its effect on lipid parameters and interfering with inflammatory and oxidative stress pathway.