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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2003-10-27
pubmed:abstractText
Despite its negative redox potential, nitroxyl (HNO) can trigger reactions of oxidation. Mechanistically, these reactions were suggested to occur with the intermediate formation of either hydroxyl radical (.OH) or peroxynitrite (ONOO-). In this work, we present further experimental evidence that HNO can generate.OH. Sodium trioxodinitrate (Na2N2O3), a commonly used donor of HNO, oxidized phenol and Me2SO to benzene diols and.CH3, respectively. The oxidation of Me2SO was O2-independent, suggesting that this process reflected neither the intermediate formation of ONOO- nor a redox cycling of transition metal ions that could initiate Fenton-like reactions. In solutions of phenol, Na2N2O3 yielded benzene-1,2-diol and benzene-1,4-diol at a ratio of 2:1, which is consistent with the generation of free.OH. Ethanol and Me2SO, which are efficient scavengers of.OH, impeded the hydroxylation of phenol. A mechanism for the hydrolysis of Na2N2O3 is proposed that includes dimerization of HNO to cis-hyponitrous acid (HO-N=N-OH) with a concomitant azo-type homolytic fission of the latter to N2 and.OH. The HNO-dependent production of.OH was with 1 order of magnitude higher at pH 6.0 than at pH 7.4. Hence, we hypothesized that HNO can exert selective toxicity to cells subjected to acidosis. In support of this thesis, Na2N2O3 was markedly more toxic to human fibroblasts and SK-N-SH neuroblastoma cells at pH 6.2 than at pH 7.4. Scavengers of.OH impeded the cytotoxicity of Na2N2O3. These results suggest that the formation of HNO may be viewed as a toxicological event in tissues subjected to acidosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42761-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12920123-Antioxidants, pubmed-meshheading:12920123-Cell Line, Tumor, pubmed-meshheading:12920123-Chromatography, High Pressure Liquid, pubmed-meshheading:12920123-Disinfectants, pubmed-meshheading:12920123-Electron Spin Resonance Spectroscopy, pubmed-meshheading:12920123-Fibroblasts, pubmed-meshheading:12920123-Humans, pubmed-meshheading:12920123-Hydrogen-Ion Concentration, pubmed-meshheading:12920123-Hydrolysis, pubmed-meshheading:12920123-Hydroxyl Radical, pubmed-meshheading:12920123-Kinetics, pubmed-meshheading:12920123-Models, Chemical, pubmed-meshheading:12920123-Nitrites, pubmed-meshheading:12920123-Nitrogen Oxides, pubmed-meshheading:12920123-Oxidants, pubmed-meshheading:12920123-Oxidation-Reduction, pubmed-meshheading:12920123-Oxygen, pubmed-meshheading:12920123-Phenol, pubmed-meshheading:12920123-Temperature, pubmed-meshheading:12920123-Time Factors
pubmed:year
2003
pubmed:articleTitle
Formation of nitroxyl and hydroxyl radical in solutions of sodium trioxodinitrate: effects of pH and cytotoxicity.
pubmed:affiliation
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.