Sitagliptin ameliorates lipid profile changes and endothelium dysfunction induced by atherogenic diet in rabbits.

The aim of this work was to investigate the effect of sitagliptin on lipid profile and endothelium function in rabbits. Rabbits were fed either normal chow or atherogenic diet for 10 weeks. Sitagliptin (6 mg/kg/twice daily) was given orally for 6 weeks starting from week 4. Blood samples were collected at day 0, week 4, and week 10 to measure serum lipid profile, nitrate/nitrite (NOx), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels. The aortic arch and thoracic aorta were excised and used for histological study and isolated vascular preparations, respectively. Sitagliptin treatment significantly reduced the levels of low density lipoprotein cholesterol, NOx, total cholesterol, and MDA, but not triglyceridess. Additionally, sitagliptin markedly reversed the decrease in high-density lipoprotein cholesterol level. Moreover, sitagliptin significantly improved the impaired endothelium-dependent relaxation, without affecting phenylepherine-induced contraction and sodium nitroprusside-induced endothelium-independent relaxation in isolated aortic rings. Histopathological examination revealed marked reduction of the atherosclerotic lesions by sitagliptin. Immunohistochemical analysis of nuclear factor-kappa B in aortic tissue showed marked reduction in its expression upon treatment with sitagliptin compared with atherogenic diet-fed rabbits. These results suggest that sitagliptin may be an effective pharmacological approach for preventing atherosclerotic lesion progression in rabbits.