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Chemical Compound Review

Peroxonitrite     oxido nitrite

Synonyms: Pernitrite, azoperoxoite, Peroxynitrate, Peroxynitrite, ONOO-, ...
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Disease relevance of Peroxonitrite


Psychiatry related information on Peroxonitrite


High impact information on Peroxonitrite

  • Although it is not fully established for all cases, the major driving force for the necrotic cell death process, and very possibly the other processes, appears to be the generation of free radicals and peroxynitrite [11].
  • Here, we show that NO-derived peroxynitrite (ONOO(-)) directly increases SERCA activity by S-glutathiolation and that this modification of SERCA is blocked by irreversible oxidation of the relevant cysteine thiols during atherosclerosis [12].
  • S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide [12].
  • ALS, SOD and peroxynitrite [13].
  • ROS (e.g., superoxide, peroxynitrite, hydroxyl radical, and hydrogen peroxide) are all potential reactants capable of initiating DNA single-strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) synthetase, leading to eventual severe energy depletion of the cells and necrotic-type cell death [3].

Chemical compound and disease context of Peroxonitrite


Biological context of Peroxonitrite


Anatomical context of Peroxonitrite


Associations of Peroxonitrite with other chemical compounds

  • IFN-gamma-driven expression of tryptophan catabolism by CTLA-4-immunoglobulin is made possible through the concomitant activation of the Forkhead Box class O (FOXO) transcription factor FOXO3a, induction of the superoxide dismutase gene, and prevention of peroxynitrite formation [27].
  • Hypochlorous acid or activated neutrophils cause decreases in the urethane-aliphatic ester stretch peak relative to the aliphatic ether stretch peak (as determined by infrared spectroscopy) whereas peroxynitrite causes selective loss of the aliphatic ether [25].
  • Both had no effect on chemical reactions associated with peroxynitrite, such as tyrosine nitration, or on the activation of inflammatory cells in vitro [28].
  • Here we establish that physiologically relevant levels of uric acid (UA), a selective inhibitor of certain peroxynitrite-mediated reactions, block the toxic effects of peroxynitrite on primary spinal cord neurons in vitro [29].
  • Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO) produced by lipopolysaccharide-stimulated cells of a mouse monocyte line [30].
  • Coadministration of morphine with the ONOO- decomposition catalyst, Fe(III) 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin, blocked protein nitration, attenuated the observed biochemical changes, and prevented the development of tolerance in a dose-dependent manner [31].
  • These results reveal an important role for free radical-mediated nitration of tyrosine residues, in apoptosis induced by endogenously produced and exogenously added peroxynitrite; moreover, tyrosine-containing peptides may offer a novel strategy to neutralize the toxic effects of peroxynitrite [32].
  • Enforced inhibition of complex III promotes the loss of Ca2+ dependence of those mitochondrial mechanisms regulating superoxide formation and mitochondrial permeability transition evoked by peroxynitrite [33].
  • Based on recent knowledge on the mechanisms of peroxynitrite decomposition and its reactions with reactive nitrogen and oxygen species, we determined Phi(1) and Phi(2) using different experimental approaches [34].
  • Recent mounting evidence implicates nitroxidative stress caused by the presence of superoxide (O(2*)(-)), nitric oxide (*NO) and subsequently peroxynitrite (ONOO(-)) in opiate analgesic tolerance [35].

Gene context of Peroxonitrite


Analytical, diagnostic and therapeutic context of Peroxonitrite

  • The defect is characterized by impaired induction of immunosuppressive tryptophan catabolism, is related to transient blockade of the signal transducer and activator of transcription (STAT)1 pathway of intracellular signaling by IFN-gamma, and is caused by peroxynitrite production [27].
  • Recent studies suggest that the neutralization of peroxynitrite or pharmacological inhibition of MMPs and PARP are promising new approaches in the experimental therapy of various forms of myocardial injury [41].
  • There was a massive activation of PARP, detected by poly(ADP-ribose) immunohistochemistry, which localized to the areas of the most severe intestinal injury, i.e., the necrotic epithelial cells at the tip of the intestinal villi, and colocalized with tyrosine nitration, an index of peroxynitrite generation [42].
  • Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts [43].
  • Peroxynitrite, the breakdown product of nitric oxide, is beneficial in blood cardioplegia but injurious in crystalloid cardioplegia [44].


  1. Nitric oxide and peroxynitrite in health and disease. Pacher, P., Beckman, J.S., Liaudet, L. Physiol. Rev. (2007) [Pubmed]
  2. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Eiserich, J.P., Hristova, M., Cross, C.E., Jones, A.D., Freeman, B.A., Halliwell, B., van der Vliet, A. Nature (1998) [Pubmed]
  3. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Cuzzocrea, S., Riley, D.P., Caputi, A.P., Salvemini, D. Pharmacol. Rev. (2001) [Pubmed]
  4. Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella from reactive nitrogen intermediates. Chakravortty, D., Hansen-Wester, I., Hensel, M. J. Exp. Med. (2002) [Pubmed]
  5. Hypoxia-reoxygenation triggers coronary vasospasm in isolated bovine coronary arteries via tyrosine nitration of prostacyclin synthase. Zou, M.H., Bachschmid, M. J. Exp. Med. (1999) [Pubmed]
  6. The physiology and pathophysiology of nitric oxide in the brain. Guix, F.X., Uribesalgo, I., Coma, M., Muñoz, F.J. Prog. Neurobiol. (2005) [Pubmed]
  7. Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection. Boven, L.A., Gomes, L., Hery, C., Gray, F., Verhoef, J., Portegies, P., Tardieu, M., Nottet, H.S. J. Immunol. (1999) [Pubmed]
  8. Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury. Lee, J.H., Yang, E.S., Park, J.W. J. Biol. Chem. (2003) [Pubmed]
  9. Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III). Pérez-De La Cruz, V., González-Cortés, C., Galván-Arzate, S., Medina-Campos, O.N., Pérez-Severiano, F., Ali, S.F., Pedraza-Chaverrí, J., Santamaría, A. Neuroscience (2005) [Pubmed]
  10. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder. Pall, M.L., Satterlee, J.D. Ann. N. Y. Acad. Sci. (2001) [Pubmed]
  11. Ischemic cell death in brain neurons. Lipton, P. Physiol. Rev. (1999) [Pubmed]
  12. S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. Adachi, T., Weisbrod, R.M., Pimentel, D.R., Ying, J., Sharov, V.S., Schöneich, C., Cohen, R.A. Nat. Med. (2004) [Pubmed]
  13. ALS, SOD and peroxynitrite. Beckman, J.S., Carson, M., Smith, C.D., Koppenol, W.H. Nature (1993) [Pubmed]
  14. Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro. Vazquez-Torres, A., Jones-Carson, J., Mastroeni, P., Ischiropoulos, H., Fang, F.C. J. Exp. Med. (2000) [Pubmed]
  15. Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus. Tanaka, K., Nakazawa, H., Okada, K., Umezawa, K., Fukuyama, N., Koga, Y. J. Clin. Invest. (1997) [Pubmed]
  16. Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. Szabó, C., Cuzzocrea, S., Zingarelli, B., O'Connor, M., Salzman, A.L. J. Clin. Invest. (1997) [Pubmed]
  17. Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury. Yu, L., Gengaro, P.E., Niederberger, M., Burke, T.J., Schrier, R.W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. Peptide methionine sulfoxide reductase from Escherichia coli and Mycobacterium tuberculosis protects bacteria against oxidative damage from reactive nitrogen intermediates. St John, G., Brot, N., Ruan, J., Erdjument-Bromage, H., Tempst, P., Weissbach, H., Nathan, C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  19. Superoxide dismutase and the death of motoneurons in ALS. Beckman, J.S., Estévez, A.G., Crow, J.P., Barbeito, L. Trends Neurosci. (2001) [Pubmed]
  20. Nitric oxide production and perivascular nitration in brain after carbon monoxide poisoning in the rat. Ischiropoulos, H., Beers, M.F., Ohnishi, S.T., Fisher, D., Garner, S.E., Thom, S.R. J. Clin. Invest. (1996) [Pubmed]
  21. Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death. Mungrue, I.N., Gros, R., You, X., Pirani, A., Azad, A., Csont, T., Schulz, R., Butany, J., Stewart, D.J., Husain, M. J. Clin. Invest. (2002) [Pubmed]
  22. Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. Lefer, D.J., Scalia, R., Campbell, B., Nossuli, T., Hayward, R., Salamon, M., Grayson, J., Lefer, A.M. J. Clin. Invest. (1997) [Pubmed]
  23. Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion. Szabó, C., Dawson, V.L. Trends Pharmacol. Sci. (1998) [Pubmed]
  24. A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice. Grohmann, U., Fallarino, F., Bianchi, R., Orabona, C., Vacca, C., Fioretti, M.C., Puccetti, P. J. Exp. Med. (2003) [Pubmed]
  25. Degradation of biomaterials by phagocyte-derived oxidants. Sutherland, K., Mahoney, J.R., Coury, A.J., Eaton, J.W. J. Clin. Invest. (1993) [Pubmed]
  26. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. Rajagopalan, S., Meng, X.P., Ramasamy, S., Harrison, D.G., Galis, Z.S. J. Clin. Invest. (1996) [Pubmed]
  27. CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic mice. Fallarino, F., Bianchi, R., Orabona, C., Vacca, C., Belladonna, M.L., Fioretti, M.C., Serreze, D.V., Grohmann, U., Puccetti, P. J. Exp. Med. (2004) [Pubmed]
  28. Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. Scott, G.S., Spitsin, S.V., Kean, R.B., Mikheeva, T., Koprowski, H., Hooper, D.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  29. Uric acid protects against secondary damage after spinal cord injury. Scott, G.S., Cuzzocrea, S., Genovese, T., Koprowski, H., Hooper, D.C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  30. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Hooper, D.C., Spitsin, S., Kean, R.B., Champion, J.M., Dickson, G.M., Chaudhry, I., Koprowski, H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  31. Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice. Muscoli, C., Cuzzocrea, S., Ndengele, M.M., Mollace, V., Porreca, F., Fabrizi, F., Esposito, E., Masini, E., Matuschak, G.M., Salvemini, D. J. Clin. Invest. (2007) [Pubmed]
  32. Prevention of peroxynitrite-induced apoptosis of motor neurons and PC12 cells by tyrosine-containing peptides. Ye, Y., Quijano, C., Robinson, K.M., Ricart, K.C., Strayer, A.L., Sahawneh, M.A., Shacka, J.J., Kirk, M., Barnes, S., Accavitti-Loper, M.A., Radi, R., Beckman, J.S., Estévez, A.G. J. Biol. Chem. (2007) [Pubmed]
  33. Inhibition of complex III promotes loss of Ca2+ dependence for mitochondrial superoxide formation and permeability transition evoked by peroxynitrite. Guidarelli, A., Cerioni, L., Cantoni, O. J. Cell. Sci. (2007) [Pubmed]
  34. Mechanism of nitrite formation by nitrate photolysis in aqueous solutions: the role of peroxynitrite, nitrogen dioxide, and hydroxyl radical. Goldstein, S., Rabani, J. J. Am. Chem. Soc. (2007) [Pubmed]
  35. Peroxynitrite: a strategic linchpin of opioid analgesic tolerance. Salvemini, D., Neumann, W.L. Trends Pharmacol. Sci. (2009) [Pubmed]
  36. Inducible nitric oxide synthase is required in alcohol-induced liver injury: studies with knockout mice. McKim, S.E., Gäbele, E., Isayama, F., Lambert, J.C., Tucker, L.M., Wheeler, M.D., Connor, H.D., Mason, R.P., Doll, M.A., Hein, D.W., Arteel, G.E. Gastroenterology (2003) [Pubmed]
  37. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. Keller, J.N., Kindy, M.S., Holtsberg, F.W., St Clair, D.K., Yen, H.C., Germeyer, A., Steiner, S.M., Bruce-Keller, A.J., Hutchins, J.B., Mattson, M.P. J. Neurosci. (1998) [Pubmed]
  38. Caspase-2 mediates neuronal cell death induced by beta-amyloid. Troy, C.M., Rabacchi, S.A., Friedman, W.J., Frappier, T.F., Brown, K., Shelanski, M.L. J. Neurosci. (2000) [Pubmed]
  39. Peroxynitrite induces integrin-dependent adhesion of human neutrophils to endothelial cells via activation of the Raf-1/MEK/Erk pathway. Zouki, C., Zhang, S.L., Chan, J.S., Filep, J.G. FASEB J. (2001) [Pubmed]
  40. iNOS-derived NO and nox2-derived superoxide confer tolerance to excitotoxic brain injury through peroxynitrite. Kawano, T., Kunz, A., Abe, T., Girouard, H., Anrather, J., Zhou, P., Iadecola, C. J. Cereb. Blood Flow Metab. (2007) [Pubmed]
  41. Nitrosative stress and pharmacological modulation of heart failure. Pacher, P., Schulz, R., Liaudet, L., Szabó, C. Trends Pharmacol. Sci. (2005) [Pubmed]
  42. Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase. Liaudet, L., Soriano, F.G., Szabó, E., Virág, L., Mabley, J.G., Salzman, A.L., Szabo, C. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  43. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. MacMillan-Crow, L.A., Crow, J.P., Kerby, J.D., Beckman, J.S., Thompson, J.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  44. Peroxynitrite, the breakdown product of nitric oxide, is beneficial in blood cardioplegia but injurious in crystalloid cardioplegia. Ronson, R.S., Thourani, V.H., Ma, X.L., Katzmark, S.L., Han, D., Zhao, Z.Q., Nakamura, M., Guyton, R.A., Vinten-Johansen, J. Circulation (1999) [Pubmed]
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