Differential and Combined Effects of Simvastatin and Vildagliptin on Angiogenic Markers and Oxidative Stress in Hind Limb Model of Ischemia in Diabetic Rats

Abstract

Background: This study investigated the potential therapeutic effect of simvastatin and vildagliptin and their combination on angiogenesis in diabetic hind-limb ischemia. Methods: 60 Sprague-dawely rats were divided into 5 groups, group A (normal control), group B (diabetic ischemic control), group C (simvastatin treated diabetic ischemic group), group D (vildagliptin treated diabetic ischemic group) and group E (combined sim. + vild. diabetic ischemic group). Parameters of angiogenesis as well as oxidative stress markers were evaluated. Results: Increased capillary density in ischemic gastrocnemius tissue of diabetic rats treated with either simvastatin or vildagliptin with marked increase in its combination. This effect was accompanied by up-regulated plasma levels of HO-1, nitric oxide, vascular endothelial growth factor (VEGF) and expression of HIF-1 alpha levels. Tissue SOD and Catalase enzymes activities were normalized in groups treated with simvastatin or their combination with vildagliptin with concomitant decrease of lipid peroxidation. Conclusion: Both vildagliptin and simvastatin has antioxidant and angiogenic effects and their combination could be a promising strategy in the management of diabetes associated peripheral arterial disease.