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

Abstract

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.

Evaluation of anti-atherosclerotic effects of Sitagliptin via modulation of the mTOR pathway in male rabbits

“…These findings agree with a previous study by Najah et al [ 21 ]. Treatment with Sitagliptin significantly reduced the levels of TC, TG, and LDL compared to the atherogenic group, consistent with the results of Sahar et al [ 15 ].…”

“…Sitagliptin, a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, has shown significant success as a monotherapy or in combination with metformin for managing type 2 diabetes by blocking the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide, which increases their beneficial effects [ 14 ]. In addition to managing diabetes, incretin enhancers such as sitagliptin may have positive effects on diabetes pathophysiology and prevent major consequences like atherosclerosis [ 15 ]. Recent research by Wenbin et al shows that sitagliptin can decrease hepatic steatosis by increasing autophagy in ob/ob mice [ 16 ].…”

Cardioprotective Effect of Quercetin and Sitagliptin in Doxorubicin-Induced Cardiac Toxicity in Rats

“… 29 , 35 The anti-inflammatory effect of quercetin has been proved in both animal and human studies, 36 and STN has also been shown to downregulate some inflammatory pathways. 37 Adding these effects together can explain the significant decrease in the level of CRP produced by the combination therapy.…”

“…Sitagliptin in previous studies has proven to have anti-atherosclerotic activity related to its ability to decrease lipid accumulation, in addition to the antioxidant and anti-inflammatory activities that aid in inhibiting the progress of atherosclerosis. 30 , 37 Quercetin also has been proven to inhibit LDL oxidation 42 and protect against atherosclerosis, 43 this can explain the effectiveness of the aforementioned combination in attenuating the atherogenic index and protecting the cardiac tissue from the deleterious effects of doxorubicin. Histopathological findings of the present study support the effectiveness of QC and STN together in reducing cardiac injury induced by DOX.…”

Cardiovascular effects of sitagliptin – An anti‐diabetes medicine

“…The anti‐atherosclerotic effects of sitagliptin have tight correlations with suppression of lipid accumulation and anti‐platelet effects, which were observed in either diabetic patients or experimental models . In hyperlipidaemic rabbits, the progression of atherosclerosis was postponed by sitagliptin treatment via reducing the production of lipid profiles . Furthermore, the regulation of platelet by sitagliptin was also reported, which might propose a potential role in the anti‐atherosclerotic of sitagliptin.…”