Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney

Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, 35294, USA.
American journal of physiology. Renal physiology (Impact Factor: 3.25). 05/2006; 290(4):F779-86. DOI: 10.1152/ajprenal.00334.2005
Source: PubMed


Reactive oxygen and nitrogen species play a key role in the pathophysiology of renal ischemia-reperfusion (I/R) injury. Recent studies have shown that nitrite (NO(2)(-)) serves as an endogenous source of nitric oxide (NO), particularly in the presence of hypoxia and acidosis. Nanomolar concentrations of NO(2)(-) reduce injury following I/R in the liver and heart in vivo. The purpose of this study was to evaluate the role of NO(2)(-) in renal I/R injury. Male Sprague-Dawley rats underwent a unilateral nephrectomy followed by 45 min of ischemia of the contralateral kidney or sham surgery under isoflurane anesthesia. Animals received normal saline, sodium NO(2)(-), or sodium nitrate (NO(3)(-); 1.2 nmol/g body wt ip) at 22.5 min after induction of ischemia or 15 min before ischemia. A separate set of animals received saline, NO(2)(-), or NO(3)(-) (0.12, 1.2, or 12 nmol/g body wt iv) 45 min before ischemia. Serum creatinine and blood urea nitrogen were increased following I/R injury but were not significantly different among treatment groups at 24 and 48 h after acute renal injury. Interestingly, NO(3)(-) administration appeared to worsen renal injury. Histological scoring for loss of brush border, tubular necrosis, and red blood cell extravasation showed no significant differences among the treatment groups. The results indicate that, contrary to the protective effects of NO(2)(-) in I/R injury of the liver and heart, NO(2)(-) does not provide protection in renal I/R injury and suggest a unique metabolism of NO(2)(-) in the kidney.

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    • "Reactive oxygen species (ROS) and nitric oxide (NO) play an important role in mediating cell damage during IR injury.[78] Inflammation contributes substantially to the pathogenesis of IR with a central role for particular cells, adhesion molecules and cytokines.[9] "
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    ABSTRACT: This study was designed to investigate the possible effect of exenatide (Glucagon like Peptide-1 receptor agonist) on liver injury (distant organ) induced by renal ischemia reperfusion (IR) in diabetic rats. In vivo renal IR was performed in both type 2 diabetic and normal rats. Each protocol comprised ischemia for 30 minutes followed by reperfusion for 24 hours and a treatment period of 14 days before induction of ischemia. Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in liver tissue were significantly increased (P < 0.01, P < 0.001, P < 0.001, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Antioxidant enzymes like glutathione, superoxide dismutase, catalase and glutathione peroxidase were significantly reduced (P < 0.05, P < 0.05, P < 0.01, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Exenatide treatment significantly normalized (P < 0.01), these biochemical parameters in treated rats compared to diabetic IR rats. Serum creatinine phosphokinase activity and liver function enzymes were also significantly normalized (P < 0.001, P < 0.001, respectively), after administration of exenatide. Exenatide exerted protective effect on exaggerated remote organ (liver) injury induced by renal IR in diabetes.
    Saudi Journal of Gastroenterology 07/2010; 16(3):174-80. DOI:10.4103/1319-3767.65187 · 1.12 Impact Factor
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    • "Thus, erythrocytes are assumed to export NO molecules, particularly at the precapillary arterioles where the P 50 of hemoglobin can most likely be achieved, provided NO bioactivity can be transported through protected mechanisms. Physiological experiments from a number of laboratories have shown that the addition of nitrite can cause downstream vasodilation and nitrite does indeed act as a vasodilator under hypoxic conditions [6] [20] [24] [41]. In addition to the nitrite reduction by hemoglobin, certain proteins in the extracellular region, such as xanthine oxidoreductase and mitochondrial proteins, can reduce nitrite to NO to regulate tissue oxygenation and other physiological functions [7] [22] [46]. "
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    ABSTRACT: Nitric oxide (NO) is a potent regulator of vascular tone and hemorheology. The signaling function of NO was largely unappreciated until approximately 30 years ago, when the endothelium-derived relaxing factor (EDRF) was identified as NO. Since then, NO from the endothelium has been considered the major source of NO in the vasculature and a contributor to the paracrine regulation of blood hemodynamics. Because NO is highly reactive, and its half-life in vivo is only a few seconds (even less in the bloodstream), any NO bioactivity derived from the intraluminal region has traditionally been considered insignificant. However, the availability and significance of NO signaling molecules derived from intraluminal sources, particularly erythrocytes, have gained attention in recent years. Multiple potential sources of NO bioactivity have been identified in the blood, but unresolved questions remain concerning these proposed sources and how the NO released via these pathways actually interacts with intravascular and extravascular targets. Here we review the hypotheses that have been put forward concerning blood-borne NO and its contribution to hemorheological properties and the regulation of vascular tone, with an emphasis on the quantitative aspects of these processes.
    Biorheology 02/2009; 46(2):107-19. DOI:10.3233/BIR-2009-0531 · 1.18 Impact Factor
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    • "Ischemia leads to hypoxia due to a decrease or stop in blood supply and thus oxygen tension and tissue pH will decrease providing more optimal conditions for nitrite reduction back to NO either through acidification/protonation or through enzymatic reduction. While nitrite has been shown to be protective in ischemia/ reperfusion (I/R) injury in the heart and liver, it was recently revealed that nitrite provides no protection in renal I/R injury [83]. This clearly demonstrates tissue-specific metabolism of nitrite. "
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    ABSTRACT: All life requires nitrogen compounds. Nitrite is such a compound that is naturally occurring in nature and biology. Over the years, the pharmacological stance on nitrite has undergone a surprising metamorphosis, from a vilified substance that generates carcinogenic nitrosamines in the stomach to a life-saving drug that liberates a protective agent (nitric oxide or NO) during hypoxic events. Nitrite has been investigated as a vasodilator in mammals for over 125 years and is a known by-product of organic nitrate metabolism. There has been a recent rediscovery of some of the vasodilator actions of nitrite in physiology along with novel discoveries which render nitrite a fundamental molecule in biology. Until recently nitrite was thought to be an inert oxidative breakdown product of endogenous NO synthesis but the past few years have focused on the reduction of nitrite back to NO in the circulation as a possible mechanism for hypoxic vasodilatation. Nitrite has evolved into an endogenous signaling molecule and regulator of gene expression that may not only serve as a diagnostic marker but also find its role as a potential therapeutic agent of cardiovascular disease. These data therefore warrant a reevaluation on the fate and metabolism of nitrite in biological systems. This review serves to encompass the history and recent evolution of nitrite, the compartment-specific metabolism of nitrite and its role in plasma as a biomarker for disease, the role of nitrite as a potential regulator of NO homeostasis, and the future of nitrite-based research.
    Free Radical Biology and Medicine 10/2006; 41(5):691-701. DOI:10.1016/j.freeradbiomed.2006.05.019 · 5.74 Impact Factor
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