الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Sildenafil citrate is a highly selective inhibitor of cyclic guanine monophosphate-specific phosphodiesterase type-5, which leads to smooth muscle relaxation and increased vascular perfusion and tissue blood flow. Clinical and experimental studies previously reported a protective effect of sildenafil in ischemic reperfusion settings. Antioxidants have been reported to reduce ischemia reperfusion injury. Selenium (Se) is one of the most important antioxidants. Antioxidant enzymes such as thioredoxin reductase (TrxR) and glutathione peroxidase along with selenoprotein-P, are responsible for the transport and storage of Se. Nano-elemental Se (SeNPs) are more biocompatible with exhibiting a dramatic decrease in toxicity. The present study investigated whether pharmacological pre-conditioning with the PDE-5 inhibitor or/and SeNPs might, through their angiogenic and antioxidant effect, respectively, reduce skeletal muscle deformation using the model of lower limb ischemia in diabetic rats. Histopathological examination revealed that treatment with combination of sildenafil and SeNPs decreased degenerative changes and inflammation in the ischemic muscle of diabetic rats. Further biochemical assessment of the hind limb tissue showed increased expression of angiogenic markers like vascular endothelial growth factor (VEGF), decreased oxidative stress markers and enhancement of the levels of heme oxygenase-1 (HO-1) with restoring inducible nitric oxide synthase (iNOS) gene expression in combined treated group. In conclusion Sildenafil and Nano selenium mediated therapeutic angiogenesis in diabetic hind limb ischemia. They improve blood supply, antioxidants delivery for cells and decrease necrosis in peripheral arterial disease (PAD). The induction of therapeutic angiogenesis by sildenafil and SeNPs achieved in this study along with resumed antioxidant defense gives hope of an alternative treatment.