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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
1997-5-8
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pubmed:abstractText |
Nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) is responsible for some of the pathophysiological alterations during inflammation. Part of NO-related cytotoxicity is mediated by peroxynitrite, an oxidant species produced from NO and superoxide. Aminoguanidine and mercaptoethylguanidine (MEG) are inhibitors of iNOS and have anti-inflammatory properties. Here we demonstrate that MEG and related compounds are scavengers of peroxynitrite. MEG caused a dose-dependent inhibition of the peroxynitrite-induced oxidation of cytochrome c2+, hydroxylation of benzoate, and nitration of 4-hydroxyphenylacetic acid. MEG reacts with peroxynitrite with a second-order rate constant of 1900 +/- 64 M-1 s-1 at 37 degrees C. In cultured macrophages, MEG reduced the suppression of mitochondrial respiration and DNA single strand breakage in response to peroxynitrite. MEG also reduced the degree of vascular hyporeactivity in rat thoracic aortic rings exposed to peroxynitrite. The free thiol plays an important role in the scavenging effect of MEG. Aminoguanidine neither affected the oxidation of cytochrome c2+ nor reacted with ground state peroxynitrite, but inhibited the peroxynitrite-induced benzoate hydroxylation and 4-hydroxyphenylacetic acid nitration, indicating that it reacts with activated peroxynitrous acid or nitrogen dioxide. Compounds that act both as iNOS inhibitors and peroxynitrite scavengers may be useful anti-inflammatory agents.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-mercaptoethylguanidine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanidines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/bis(2-guanidinoethyl)disulfide,
http://linkedlifedata.com/resource/pubmed/chemical/peroxynitric acid,
http://linkedlifedata.com/resource/pubmed/chemical/pimagedine
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9030-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9083027-Animals,
pubmed-meshheading:9083027-Cell Line,
pubmed-meshheading:9083027-Enzyme Inhibitors,
pubmed-meshheading:9083027-Guanidines,
pubmed-meshheading:9083027-Kinetics,
pubmed-meshheading:9083027-Models, Chemical,
pubmed-meshheading:9083027-Muscle, Smooth, Vascular,
pubmed-meshheading:9083027-Muscle Contraction,
pubmed-meshheading:9083027-Nitrates,
pubmed-meshheading:9083027-Nitric Oxide Synthase,
pubmed-meshheading:9083027-Norepinephrine,
pubmed-meshheading:9083027-Oxidation-Reduction,
pubmed-meshheading:9083027-Oxygen Consumption,
pubmed-meshheading:9083027-Rats,
pubmed-meshheading:9083027-Vasoconstrictor Agents
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pubmed:year |
1997
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pubmed:articleTitle |
Mercaptoethylguanidine and guanidine inhibitors of nitric-oxide synthase react with peroxynitrite and protect against peroxynitrite-induced oxidative damage.
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pubmed:affiliation |
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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