Beneficial Effects ofN-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Abstract

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague-Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

Oxidant Mechanisms in Renal Injury and Disease

“…Ebselen is an antioxidant that scavenges peroxynitrite without effecting endogenous nitric oxide (195), making this antioxidant very attractive for treatment of oxidative stress-related pathological conditions. In various animal models of AKI, ebselen application prevented lipid peroxidation, enhanced endothelial and epithelial cell viability, and improved renal function (35,39,58,94,150,207,223,228). However, the benefits of ebselen remain to be seen in human subjects.…”

“…Other compounds that target the mitochondria have gained interest in recent years for treatment of kidney injury and disease, including mitoquinone mesylate (a derivative of CoQ10, termed MitoQ) and a-tocopherol-conjugated triphenylphosphonium (otherwise referred to as MitoVit E or mitochondrial targeted vitamin E). Animal studies with MitoQ have shown its ability to improve renal function during diabetic nephropathy, toxin-induced nephropathy, and IRI-induced AKI (34, 58,150,223). However, it remains to be seen if MitoQ improves renal function in human CKD patients.…”

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Renal Injury in Rats

“…All of these hazardous events can lead to undesirable conditions, including hypertension and renal failure [11]. Although, several antioxidants and anti-inflammatory agents have been used to prevent or decrease the kidney damage that can be caused by I/R injury [12][13][14][15], there have been no studies on the protective and therapeutic effects of dexpanthenol (Dxp) against renal I/R injury.…”

Hyperbaric Oxygen Therapy Alleviates Oxidative Stress and Tissue Injury in Renal Ischemia/Reperfusion Injury in Rats

“…Restoration of blood flow after a period of ischemia may further increase the initial damage via release of oxygen free radicals [reactive oxygen species (ROS)]. 2 Free radicals react with almost all biomolecules including nucleic acids, proteins, lipids, carbohydrates, and connective tissue macromolecules and cause reversible or irreversible changes in the structure of these molecules. 3 While small amounts of free radicals are formed during ischemia, much larger amounts are formed in the reperfusion period.…”

“…4 Free radical scavengers are one of the main focuses of current ischemia/reperfusion (I/R) research, but an effective treatment ready to use in routine practice has not been found yet. 2,5,6 Hyperbaric oxygen (HBO) therapy involves the intermittent inhalation of 100% of oxygen under a pressure greater than 1 atm. HBO therapy increases the dissolved oxygen concentration in the arterial blood and enhances the rate of diffusion of oxygen into poorly perfused tissues.…”