Hydrogen sulfide regulates cardiac function and structure in adriamycin-induced cardiomyopathy

Circ J. 2009 Apr;73(4):741-9. doi: 10.1253/circj.cj-08-0636. Epub 2009 Feb 27.

Abstract

Background: The present study was designed to investigate if hydrogen sulfide (H2S), a novel gasotransmitter, might have a regulatory effect on cardiac function and structure, as well as oxidative stress, in adriamycin (ADR)-induced cardiomyopathy.

Methods and results: Hemodynamic measurements, histopathological examination and stereological ultrastructural analysis of mitochondria in ADR-treated rats showed characteristics of cardiomyopathy with remarkable greater size and smaller number of cardiomyocytic mitochondria and a significantly low H2S content in plasma and myocardium, but increased levels of thiobarbituric acid reactive substance (TBARs) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma and myocardium compared with controls (P<0.01). However, administration of the H2S donor, NaHS, markedly improved cardiac function, as demonstrated by elevated left ventricular developed pressure (+/-LVdp/dtmax; P<0.01) with ameliorated morphological alterations in the myocardium. Myocardial TBARs content decreased, whereas the activities of SOD and GSH-Px increased (P<0.01 and P<0.05, respectively).

Conclusions: Downregulation of endogenously-generated H2S is probably involved in the pathogenesis of ADR-induced cardiomyopathy, whereby H2S reduces lipid peroxidation, increases antioxidation, and inhibits oxidative stress injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / pharmacology
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / pathology*
  • Doxorubicin / adverse effects*
  • Doxorubicin / pharmacology
  • Hydrogen Sulfide / metabolism*
  • Male
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Sulfides / pharmacology
  • Superoxide Dismutase / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Sulfides
  • Doxorubicin
  • Superoxide Dismutase
  • sodium bisulfide
  • Hydrogen Sulfide