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Back ground: Atherosclerosis is the major cause of death. The most common risk factors are hyperlipidemia, diabetes, and other factors like chronic infection and inflammation. Objective: This study was undertaken to assess the effect of sitagliptin on atherosclerosis via interfering with inflammatory and oxidative pathways. Materials and Methods: A total of 18 local domestic male rabbits were included in this study. The animals were randomly divided into three groups (6 rabbits in each group): Group I normal were fed with chow (oxiod) diet for 12 weeks. Group II were fed with 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 sitagliptin 125 mg/kg/day orally for the next 6 weeks. Blood samples were collected at the start of the study, at 6 weeks of the study and then at the end of treatment to measure serum lipids profile, hsCRP and TNFα. At end of the study, the aorta was removed for measurement of MDA, glutathione and, aortic intima-media thickness. Results: Sitagliptin results in a significant reduction (p < 0.05) in serum level of total cholesterol (TC), triglycerides (TG), high sensitive C-reactive protein (hsCRP) and TNFα with a significant increase (p < 0.05) in serum HDL level. There was a significant reduction (p < 0.05) in aortic MDA, in comparison to the untreated control group. Furthermore, sitagliptin causes significant increment (p < 0.05) in aortic GSH in comparison to induced untreated group. Regarding histopathological results, sitagliptin 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). Conclusion: Sitagliptin reduced atherosclerosis progression in hyperlipidemic rabbit via its effect on lipid parameters and interfering with inflammatory and oxidative stress

Sitagliptin ameliorates the progression of atherosclerosis via down regulation of the inflammatory and oxidative pathways