Protective action of cardiac DT-diaphorase against menadione toxicity in guinea pig isolated atria

Maura Floreani, Eleonora Napoli, Pietro Palatini

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 (β-naphthoflavone) of the enzyme on the inotropic action of the quinone. In electrically driven left atria of guinea pig, 4 μM 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 β-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 β-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. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)601-605
Number of pages5
JournalBiochemical Pharmacology
Volume60
Issue number4
DOIs
StatePublished - Aug 15 2000
Externally publishedYes

Keywords

  • β-Naphthoflavone
  • Dicoumarol
  • DT-diaphorase
  • Guinea pig atria
  • Menadione
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology

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