Abstract
Background: Atherosclerosis is a progressive disease of large and medium-sized arteries characterized by the accumulation of lipids and fibrous elements in the large arteries. Aim of the study: This study was undertaken to assess the effect of vildagliptin on the progression of atherosclerosis via interfering with inflammatory and oxidative pathways. Materials and Methods: 18 local domestic male rabbits were included in this study. The animals were randomly divided into three groups (6 rabbits for 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 50 mg/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 thickness. Results: 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 the 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.
Highlights
Atherosclerosis is a progressive disease of large and medium-sized arteries characterized by the accumulation of lipids and fibrous elements in the large arteries
Blood samples were collected at the start of the study, at 6weeks of the study and at the end of treatment course for measurement of Serum lipids profile [total cholesterol (TC), serum triglyceride (TG) and high density lipoprotein (HDL)], high sensitive C-reactive protein, tumor necrosis factor (TNFα) at the end of the study the aorta were removed for measurement of aortic malonyl dehydrogenase (MDA), glutathione (GSH) and Aortic intima- media thickness and sectioning for histopathology
At the end of 12 weeks, there was a statistically significant increase in serum TC level (P
Summary
Atherosclerosis is a progressive disease of large and medium-sized arteries characterized by the accumulation of lipids and fibrous elements in the large arteries. The role of the gastrointestinal tract in regulating the secretion of insulin is demonstrated by the thought that insulin secretion is substantially increased in response to oral glucose load, compared to intravenous glucose administration. This difference is known as the incretin effect; these peptides are secreted from endocrine cells (L-cells) in the gastrointestinal tract, and are released in response to ingestion of food and subsequent oral glucose load.
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