Source:http://linkedlifedata.com/resource/pubmed/id/10874136
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2000-8-21
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pubmed:abstractText |
In myocardial preparations isolated from guinea pigs, 2-methyl-1, 4-naphthoquinone (menadione) causes an increase in contractility that is strictly related to the generation of reactive oxygen species (ROS) as a consequence of quinone metabolism. In heart, menadione undergoes one-electron reduction to semiquinone, a reaction mainly catalysed by mitochondrial NADH: ubiquinone oxidoreductase. It is also converted to hydroquinone by the soluble two-electron reductase, DT-diaphorase, and is conjugated with GSH by glutathione S-transferase. In order to assess the role of DT-diaphorase in cardiac responses to menadione, we examined the effects of both a specific inhibitor (dicoumarol) and an inducer (beta-naphthoflavone) of the enzyme on the inotropic action of the quinone. In electrically driven left atria of guinea pig, 4 microM dicoumarol significantly enhanced the positive inotropic effect of menadione, especially at the lower concentrations of the quinone. In myocardial preparations isolated from guinea pigs treated with beta-naphthoflavone (80 mg/kg i.p.for 2 days), DT-diaphorase activity was enhanced (+36% with respect to control animals, P < 0. 01), whereas the activities of the other enzymes involved in menadione metabolism were not modified. In these preparations, menadione caused a significantly lower increase in the force of contraction than in atria from untreated animals; moreover, pretreatment with beta-naphthoflavone caused a significant decrease in the menadione-induced oxidative stress, as evaluated from the GSH redox index. Taken together, these results demonstrate that cardiac DT-diaphorase does not contribute to ROS generation, but represents a detoxification system.
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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/Dicumarol,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Methylcholanthrene,
http://linkedlifedata.com/resource/pubmed/chemical/NAD(P)H Dehydrogenase (Quinone),
http://linkedlifedata.com/resource/pubmed/chemical/Protective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin K,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Naphthoflavone
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
601-5
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10874136-Analysis of Variance,
pubmed-meshheading:10874136-Animals,
pubmed-meshheading:10874136-Dicumarol,
pubmed-meshheading:10874136-Dose-Response Relationship, Drug,
pubmed-meshheading:10874136-Drug Interactions,
pubmed-meshheading:10874136-Enzyme Inhibitors,
pubmed-meshheading:10874136-Guinea Pigs,
pubmed-meshheading:10874136-Heart Atria,
pubmed-meshheading:10874136-Male,
pubmed-meshheading:10874136-Methylcholanthrene,
pubmed-meshheading:10874136-NAD(P)H Dehydrogenase (Quinone),
pubmed-meshheading:10874136-Protective Agents,
pubmed-meshheading:10874136-Reactive Oxygen Species,
pubmed-meshheading:10874136-Vitamin K,
pubmed-meshheading:10874136-beta-Naphthoflavone
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pubmed:year |
2000
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pubmed:articleTitle |
Protective action of cardiac DT-diaphorase against menadione toxicity in guinea pig isolated atria.
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pubmed:affiliation |
Department of Pharmacology, University of Padova, Padova, Italy. floreani@ux1.unipd.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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