Nephroprotective Potential Effect of Azilsartan in Renal Ischemia Reperfusion Injury /role VEGF Pathway

Abstract

Aseel Noaman Ali, Murooj L. Altimimi, Haider Mahdi Al-Ardi,Najah R Hadi

The impairment of blood flow to the kidney causes renal injury occurs by ischemia/reperfusion in surgical procedures, in which the kidneys remainwithout blood supply for some time. This is observed during kidney transplantation, vascular surgery of aorta and renal arteries, and in partial nephrectomy. Inflammation is major contributor to the pathogenesis of renal ischemia/reperfusion in acute kidney injury with an endothelium loss, causing the vascular dysfunction and the angiogenesis deregulation. Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension. It demonstrates organ protective effects in hypertension. In this study, we aim to assess the ability of azilsartanto exert potential protective effects on the kidney I/R and subsequent kidney dysfunctions in the rat through the modulation of pro?inflammatory cytokinesand angiogenesis parameters (vascular endothelial growth factor receptor2 /vascular endothelial growth factor pathway). A total of 24 rats were randomly distributed into 4 groups (6 rats in each one) then they used in this experiment and the ischemia-reperfusion injury was induced in a rat model by bilateral renal artery clamping for 30 min and reperfusion for 2 h, and azilsartan (0.4 mg/kg) and vehicle was injected through intraperitoneally route before 30 min. prior of ischemia-reperfusion injury induction. Azilsartan administration could exert a protective role in the kidney against injury by significantly reducing the tissue levels of pro?inflammatory cytokines (interleukin 1 beta, Monocyte chemoattractant protein-1and high mobility group box protein 1), lessen the serum levels of renal function parameters (blood urea nitrogen and serum creatinine), reduction of the histopathological severity score of renal damage and up regulation the angiogenesis markers (Vascular endothelial growth factor receptor 2, caveolin-1 and cluster of differentiation 34). All changes in the study parameters were significant (p value≤ 0.05).