الفهرس 
Title : Study on the effect of saxagliptin on renal injury induced by ischemia/reperfusion in rats
AbstractOnly 14 pages are availabe for public view
 |  | from | 136 |  |  |
| | | from | 136 | | |
Abstract
Saxagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, is currently used in type 2 diabetes mellitus; however, its potential role against the renal ischemia/reperfusion (I/R) insult has not been elucidated. Using the renal I/R model in Wistar rats, saxagliptin (10 and 30 mg/kg) operated through different axes to enhance renal perfusion, it increased the renal kidney injury molecule-1/p-STAT3 (Tyr705)/hypoxia inducible factor-1Ü/vascular endothelial growth factor (VEGF) pathway to enhance angiogenesis. Additionally, by inhibiting DPP-4, saxagliptin spared the stromal cell derived factor-1Ü and increased its receptor, the chemokine receptor (CXCR) 4, to trigger vasculogenesis by enhancing the migration of endothelial progenitor cells (EPCs), designated by the elevated immunoreactive CD133+ cells. The gliptin also saved glucagon like peptide-1, with the subsequent increase in cAMP that positively influenced VEGF and CXCR4. Another pathway stimulated by saxagliptin was the atrial natriuretic peptide/endothelial nitric oxide synthase that increased nitric oxide to provoke angiogenesis and renal vasodilation. These interrelated molecules improved kidney function of rats subjected to acute renal I/R, as evidenced by the decreased serum creatinine, blood urea nitrogen, and cystatin C, increased serum albumin, and improved the histological structure. Additionally, saxaglipitin suppressed the renal phosphor-serine 536 nuclear factor-mB p65, monocyte chemoattractant protein-1, myeloperoxidase, malondialdehyde, and tumor necrosis factor-Ü, while boosted glutathione. Accordingly, saxagliptin, dose dependently, ameliorated I/R-induced renal damage via its anti-inflammatory and antioxidant activities, besides the enhancement of neovascularization through improving tissue perfusion and homing of bone marrow derived EPCs to intercede repair processes