Abstract

Background/aimSince the nature of ischemia/reperfusion (IR)-induced tissue damage is multifactorial and complex, in the current study, the effects of multiple treatment strategies via concomitant administration of erythropoietin (EPO) and N-acetylcysteine (NAC) with an ischemic preconditioning (IPC) regimen on renal IR injury were examined.Materials and methods Thirty male Wistar rats were subjected to bilateral occlusion of the renal pedicles for 50 min followed by reperfusion. EPO (1000 IU/kg) was administered for 3 days, as well as IPC before the IR and NAC (150 mg/kg) administration for 4 days after IR. The animals were randomly allocated into 6 groups (n = 5): sham, IR, EPO+IR, IPC+IR, NAC+IR, and EPO+IPC+NAC+IR. Kidney tissues and blood samples were obtained for oxidative stress, proinflammatory cytokines, and renal functional evaluations.Results IR caused significant inflammatory response, oxidative stress, and reduced renal function. Treatment with EPO, IPC, and NAC or a combination of two of them attenuated renal dysfunction and reduced the oxidative stress and inflammatory markers. Rats treated with the combination of EPO, IPC, and NAC showed a higher degree of protection compared to the other groups.Conclusion These results showed that concomitant administration of EPO and IPC along with posttreatment NAC may have additive beneficial effects on kidney IR injury during IR-induced acute renal failure.

Highlights

  • Acute renal failure as a result of ischemia/reperfusion (IR) injury refers to a pathophysiological process by which renal ischemic cells become more damaged following the restoration of the blood supply [1]

  • Rats treated with the combination of EPO, ischemic preconditioning (IPC), and NAC showed a higher degree of protection compared to the other groups

  • These results showed that concomitant administration of EPO and IPC along with posttreatment NAC may have additive beneficial effects on kidney IR injury during IR-induced acute renal failure

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Summary

Introduction

Acute renal failure as a result of ischemia/reperfusion (IR) injury refers to a pathophysiological process by which renal ischemic cells become more damaged following the restoration of the blood supply [1]. IR injury as the main cause of acute renal failure occurs subsequent to different kinds of acute stress, including kidney vascular surgery, transplantation, septic shock, trauma, extracorporeal shock wave lithotripsy, or resuscitation [2]. Inflammation, apoptosis, necrosis, and the formation of reactive oxygen species (ROS) have been suggested to be involved in the pathogenesis of IR injury [4]. The modulation of inflammatory response, inhibition of apoptosis, and amelioration of oxidative stress confer an advantage in the prevention and treatment of renal IR injury [5]. Several interventional mechanisms and Erythropoietin (EPO) is a hematopoietic growth factor released by the kidney in response to hypoxia, inflammation, and cell death [7]. EPO has been suggested to exert antioxidant, antiinflammatory, and antiapoptotic effects against kidney IR injury [7,8]

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