Antioxidative and Anti-Inflammatory Impact of Valsartan Against Renal Ischemia-Reperfusion Injury; Role of Nitric Oxide Signaling Pathway Publisher



Mohmoodnia L¹ ; Ahmadvand SS² ; Koushki S² ; Farzan B³ ; Papi S⁴ ; Hadian B⁵ ; Dehpour AR^{6, 7} ; Hasanvand A⁸ Show Affiliations
Source: Immunopathologia Persa Published:2019

Abstract

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220±10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects. Copyright © 2019 The Author(s); Published by Nickan Research Institute.