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Journal ArticleDOI

Oxidative stress and reactive nitrogen species generation during renal ischemia.

01 Sep 2001-Toxicological Sciences (Oxford University Press)-Vol. 63, Iss: 1, pp 143-148
TL;DR: The data clearly demonstrate that oxidative stress and RNS generation occur in the kidney during ischemia, and indicates that reactive nitrogen species (RNS) formation during I-R injury is driven by oxidant stress.
About: This article is published in Toxicological Sciences.The article was published on 2001-09-01 and is currently open access. It has received 106 citations till now. The article focuses on the topics: Renal ischemia & Reperfusion injury.
Citations
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Journal ArticleDOI
TL;DR: Inhalation of hydrogen gas is proposed as a widely applicable method to reduce oxidative stress and reduced levels of serum alanine aminotransferase and hepatic malondialdehyde, and helium gas showed no protective effect, suggesting that the protective effect by hydrogenGas is specific.

367 citations


Cites background from "Oxidative stress and reactive nitro..."

  • ...Moreover, when tissues are exposed to ischemia followed by reperfusion (I/R), ROS are extensively generated in the early stage of reperfusion to cause serious damage to tissues in various organs, including the liver [1], brain [2], heart [3], and kidney [4]....

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Journal ArticleDOI
TL;DR: Using a proteomics approach, enolase, glyceraldehyde-3-phosphate dehydrogenase, ATP synthase alpha chain, carbonic anhydrase-II, and voltage-dependent anion channel-protein are identified as the targets of nitration in AD hippocampus, a region that shows a extensive deposition of amyloid beta-peptide compared with the age-matched control brains.

353 citations


Cites background from "Oxidative stress and reactive nitro..."

  • ..., 1998), amyotrophic lateral sclerosis (ALS) (Cookson and Shaw, 1999), and ischemia–reperfusion (Hall et al., 1995a,b, 2004; Walker et al., 2001; Zou and Bachschmid, 1999)....

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  • ...…AD (Smith et al., 1997, Tohgi et al., 1999; Castegna et al., 2003; Hensley et al., 1998), Parkinson’s disease (PD) (Good et al., 1998), amyotrophic lateral sclerosis (ALS) (Cookson and Shaw, 1999), and ischemia–reperfusion (Hall et al., 1995a,b, 2004; Walker et al., 2001; Zou and Bachschmid, 1999)....

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Journal ArticleDOI
TL;DR: The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity and may be particularly important in renal injury patients with low vitamin C status.
Abstract: Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status.

174 citations


Cites background from "Oxidative stress and reactive nitro..."

  • ...Lipid peroxidation and DNA damage in ischemia are associated with the formation of 3-nitrotyrosine, a biomarker for ROS/RNS, suggesting that NO•, O2•−, and/or peroxynitrite, contribute to renal oxidative damage [18,19]....

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  • ...An imbalance in NO• and O2 production during hypoxia and I/R injury may contribute to renal cell damage [18,19]....

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  • ...Lipid peroxidation and DNA damage in ischemia are associated with the formation of 3-nitrotyrosine, a biomarker for ROS/R S, suggesting that NO•, O2, and/or peroxynitrite, contribute to renal oxidative damage [18,19]....

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Journal ArticleDOI
TL;DR: Resveratrol may have a dual mechanism of action to restore the renal microcirculation and scavenge reactive nitrogen species, thus protecting the tubular epithelium even when administered after the onset of sepsis.

165 citations

Journal ArticleDOI
TL;DR: The data reveal that protein tyrosine nitration in mitochondria can be controlled, is target-selective and rapid, and is dynamic enough to serve as a nitrative regulatory signaling process that likely affects cellular energy, redox homeostasis, and pathological conditions when these features become disturbed.

164 citations

References
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Journal ArticleDOI
TL;DR: This review provides a comprehensive summary on the chemical properties of 4-hydroxyalkenals and malonaldehyde, the mechanisms of their formation and their occurrence in biological systems and methods for their determination, as well as the many types of biological activities described so far.

6,456 citations

Journal ArticleDOI
18 Dec 1992-Science
TL;DR: The integration of this chemistry with current perspectives of NO biology illuminates many aspects of NO biochemistry, including the enzymatic mechanism of synthesis, the mode of transport and targeting in biological systems, the means by which its toxicity is mitigated, and the function-regulating interaction with target proteins.
Abstract: Nitric oxide (NO.), a potentially toxic molecule, has been implicated in a wide range of biological functions. Details of its biochemistry, however, remain poorly understood. The broader chemistry of nitrogen monoxide (NO) involves a redox array of species with distinctive properties and reactivities: NO+ (nitrosonium), NO., and NO- (nitroxyl anion). The integration of this chemistry with current perspectives of NO biology illuminates many aspects of NO biochemistry, including the enzymatic mechanism of synthesis, the mode of transport and targeting in biological systems, the means by which its toxicity is mitigated, and the function-regulating interaction with target proteins.

2,713 citations

Journal ArticleDOI
01 Jan 1993
TL;DR: The rate constant for the reaction of NO with .O2- was determined to be (6.7 +/- 0.9) x 10(9) l mol-1 s-1, considerably higher than previously reported.
Abstract: The rate constant for the reaction of NO with ·O2− was determined to be (6.7 ± 0.9) × 109 1 mol−1 s−1, considerably higher than previously reported. Rate measurements were made from pH 5.6 to 12.5 ...

2,113 citations


"Oxidative stress and reactive nitro..." refers background in this paper

  • ...The reaction is extremely fast and will occur at a near diffusion-limited rate (Huie and Padmaja, 1993)....

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Journal ArticleDOI
TL;DR: The cage mechanism can explain the residual yield of nitrate that appears to be formed even in the presence of high concentrations of all of the scavengers studied to date, since scavengers capture only free HO. and .NO2 and not caged radicals.
Abstract: Nitric oxide and superoxide, which are produced by several cell types, rapidly combine to form peroxynitrite. This reaction can result in nitric oxide scavenging, and thus mitigation of the biological effects of superoxide. Also, superoxide can trap and hence modulate the effects of nitric oxide; superoxide dismutase, by controlling superoxide levels, therefore can influence the reaction pathways open to nitric oxide. The production of peroxynitrite, however, causes its own sequelae of events: Although neither .NO nor superoxide is a strong oxidant, peroxynitrite is a potent and versatile oxidant that can attack a wide range of biological targets. The peroxynitrite anion is relatively stable, but its acid, peroxynitrous acid (HOONO), rearranges to form nitrate with a half-life of approximately 1 s at pH 7, 37 degrees C. HOONO exists as a Boltzmann distribution of rotamers; at 5-37 degrees C HOONO has an apparent acidity constant, pKa,app, of 6.8. Oxidation reactions of HOONO can involve two-electron processes (such as an SN2 displacement) or a one-electron transfer (ET) reaction in which the substrate is oxidized by one electron and peroxynitrite is reduced. These oxidation reactions could involve one of two mechanisms. The first mechanism is homolysis of HOONO to give HO. and .NO2, which initially are held together in a solvent cage. This caged pair of radicals (the "geminate" pair) can either diffuse apart, giving free radicals that can perform oxidations, or react together either to form nitrate or to reform HOONO (a process called cage return). A large amount of cage return can explain the small entropy of activation (Arrhenius A-factor) observed for the decomposition of HOONO. A cage mechanism also can explain the residual yield of nitrate that appears to be formed even in the presence of high concentrations of all of the scavengers studied to date, since scavengers capture only free HO. and .NO2 and not caged radicals. If the cage mechanism is correct, the rate of disappearance of peroxynitrite be slower in solvents of higher viscosity, and we do not find this to be the case. The second mechanism is that an activated isomer of peroxynitrous acid, HOONO*, can be formed in a steady state. The HOONO* mechanism can explain the inability of hydroxyl radical scavengers to completely block either nitrate formation or the oxidation of substrates such as methionine, since HOONO* would be less reactive, and therefore more selective, than the hydroxyl radical itself.(ABSTRACT TRUNCATED AT 400 WORDS)

1,526 citations


"Oxidative stress and reactive nitro..." refers background in this paper

  • ...ONOO– is a potent and versatile oxidant that can react with cellular lipids, proteins, and DNA (Pryor and Squadrito, 1995)....

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  • ...ONOO is a potent and versatile oxidant that can react with cellular lipids, proteins, and DNA (Pryor and Squadrito, 1995)....

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Journal ArticleDOI
TL;DR: The oxygen free radical scavengers SOD and DMTU, and allopurinol, which inhibits free radical generation, protected renal function after ischemia, and restoration of oxygen supply to ischemic kidney results in the production of oxygen free radicals, which causes renal injury by lipid peroxidation.
Abstract: During renal ischemia, ATP is degraded to hypoxanthine. When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radical (O-2) is generated. We studied the role of O-2 and its reduction product OH X in mediating renal injury after ischemia. Male Sprague-Dawley rats underwent right nephrectomy followed by 60 min of occlusion of the left renal artery. The O-2 scavenger superoxide dismutase (SOD) was given 8 min before clamping and before release of the renal artery clamp. Control rats received 5% dextrose instead. Plasma creatinine was lower in SOD treated rats: 1.5, 1.0, and 0.8 mg/dl vs. 2.5, 2.5, and 2.1 mg/dl at 24, 48, and 72 h postischemia. 24 h after ischemia inulin clearance was higher in SOD treated rats than in controls (399 vs. 185 microliter/min). Renal blood flow, measured after ischemia plus 15 min of reflow, was also greater in SOD treated than in control rats. Furthermore, tubular injury, judged histologically in perfusion fixed specimens, was less in SOD treated rats. Rats given SOD inactivated by prior incubation with diethyldithiocarbamate had plasma creatinine values no different from those of control rats. The OH X scavenger dimethylthiourea (DMTU) was given before renal artery occlusion. DMTU treated rats had lower plasma creatinine than did controls: 1.7, 1.7, and 1.3 mg/dl vs. 3.2, 2.2, and 2.4 mg/dl at 24, 48, and 72 h postischemia. Neither SOD nor DMTU caused an increase in renal blood flow, urine flow rate, or solute excretion in normal rats. The xanthine oxidase inhibitor allopurinol was given before ischemia to prevent the generation of oxygen free radicals. Plasma creatinine was lower in allopurinol treated rats: 2.7, 2.2, and 1.4 mg/dl vs. 3.6, 3.5, and 2.3 mg/dl at 24, 48, and 72 h postischemia. Catalase treatment did not protect against renal ischemia, perhaps because its large size limits glomerular filtration and access to the tubular lumen. Superoxide-mediated lipid peroxidation was studied after renal ischemia. 60 min of ischemia did not increase the renal content of the lipid peroxide malondialdehyde, whereas ischemia plus 15 min reflow resulted in a large increase in kidney lipid peroxides. Treatment with SOD before renal ischemia prevented the reflow-induced increase in lipid peroxidation in renal cortical mitochondria but not in crude cortical homogenates. In summary, the oxygen free radical scavengers SOD and DMTU, and allopurinol, which inhibits free radical generation, protected renal function after ischemia. Reperfusion after ischemia resulted in lipid peroxidation; SOD decreased lipid peroxidation in cortical mitochondria after renal ischemia and reflow. We concluded that restoration of oxygen supply to ischemic kidney results in the production of oxygen free radicals, which causes renal injury by lipid peroxidation.

978 citations


"Oxidative stress and reactive nitro..." refers background in this paper

  • ...Despite the fact that numerous antioxidants afford some degree of protection against renal I-R injury (De Vecchi et al., 1998; Paller and Hedlund, 1988; Paller et al., 1984), the role of oxidants in the development of acute renal failure due to I-R remains controversial because direct evidence of hydroxyl radial formation is lacking (Zager et al....

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