Demonstration of hydroxyl radical and its role in hydrogen peroxide-induced myocardial injury: Hydroxyl radical dependent and independent mechanisms

Genzou Takemura, Tomoya Onodera, Ronald W. Millard, Muhammad Ashraf

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We investigated the mechanism of hydrogen peroxide (H2O2) action on myocardial injury in relation to hydroxyl radical (OH) formation. Isolated rat hearts were perfused with a concentration of H2O2 (300 μM) known to produce cardiac injury. Perfusion of H2O2 for 15 min caused severe myocardial dysfunction, morphological damage. ATP depletion, and lipid peroxidation. Hydrogen peroxide concentration in the coronary effluent was reduced approximately 40% reflecting a myocardial H2O2 consumption of 12.7 ± 0.9 μmol/15 min/g wet tissue (n = 12). One of the OH-generated derivatives, 2,3-dihydroxybenzoic acid (2,3-DHBA), formed from reaction with salicylic acid, was detected in the coronary effluent by high-performance liquid chromatography at 23.16 ± 4.05 nmol/15 min/g wet tissue. Catalase (200 U/ml, n = 6) added to the perfusate attenuated all parameters of myocardial injury by eliminating H2O2 from the perfusate, and thus OH was not detected in the effluent. Deferoxamine (5 mM, n = 7) added to the perfusate reduced morphological damage and lipid peroxidation, but not dysfunction or ATP depletion. Deferoxamine significantly reduced OH production; 2,3-DHBA was 5.22 ± 3.56 nmol/15 min/g wet tissue. The present study provides evidence that OH is produced in the H2O2-perfused heart. The adverse H2O2-mediated myocardial outcomes documented in this study appear to arise from both OH-dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)13-25
Number of pages13
JournalFree Radical Biology and Medicine
Volume15
Issue number1
DOIs
Publication statusPublished - Jul 1993
Externally publishedYes

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Keywords

  • ATP
  • Free radicals
  • Function
  • Hydrogen peroxide
  • Hydroxyl radical
  • Lipid peroxidation
  • Myocardium
  • Rat
  • Salicylic acid
  • Ultrastructure

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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