The protective role of hydrogen sulfide in myocardial ischemia-reperfusion-induced injury in diabetic rats

Int J Cardiol. 2011 Oct 20;152(2):177-83. doi: 10.1016/j.ijcard.2010.07.012. Epub 2011 Feb 12.

Abstract

Background: Hydrogen sulfide (H(2)S) displays anti-inflammatory and cytoprotective activities to attenuate myocardial ischemia-reperfusion (MIR)-induced injury, but its role in MIR in diabetics is not known. This study was undertaken to investigate whether H(2)S plays a protective role in MIR in diabetic rats.

Methods: Diabetes was induced by streptozocin in Wistar rats, which were subjected to myocardial ischemia by blocking the left circumflex artery for 30 min, followed by 2h reperfusion. dl-propargylglycine (PAG) and sodium hydrosulfide (NaHS) were administered to the rats to investigate their effects on severity of MIR-induced injury.

Results: Diabetic rats had smaller myocardial infarct sizes and higher serum levels of H(2)S (both P < 0.05) than non-diabetics when they underwent MIR. MIR significantly increased the serum level of H(2)S (49.5 ± 7.1 μM), H(2)S-synthesizing activity (7.4 ± 1.6 nmol/mg) and the myocardial infarct size (44.0 ± 7.2%), compared with sham-operated diabetic rats (21.7 ± 2.1 μM, 0.15 ± 0.4 nmol/mg and 1.2 ± 0.4%, respectively). Administration of NaHS increased the H(2)S level (65.8 ± 6.9 μM) and had little effect on H(2)S production activity (6.5 ± 2.2 nmol/mg), while PAG reduced both the H(2)S level (29.2 ± 5.0 μM) and H(2)S-synthesizing activity (2.2 ± 1.8 nmol/mg). NaHS significantly reduced the myocardial infarct size (31.2 ± 4.7%), inhibited the production of lipid peroxidation, MPO activity, and cell apoptosis, and downregulated expression of caspase-3, Fas, FasL, and TNF-α, which had been elevated by MIR, while PAG further increased the myocardial infarct size (58.3 ± 5.9%), and displayed opposite effects.

Conclusions: The study indicates that H(2)S may play a protective role in MIR-induced myocardial injury in diabetics by its anti-apoptotic, anti-oxidative and anti-inflammatory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Diabetes Mellitus, Experimental*
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology
  • Fas Ligand Protein / metabolism
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hydrogen Sulfide / blood
  • Hydrogen Sulfide / pharmacology*
  • Lipid Peroxidation / drug effects
  • Male
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / metabolism*
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Sulfides / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • fas Receptor / metabolism

Substances

  • Alkynes
  • Enzyme Inhibitors
  • Fas Ligand Protein
  • Fas protein, rat
  • Faslg protein, rat
  • Sulfides
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • propargylglycine
  • Peroxidase
  • Caspase 3
  • sodium bisulfide
  • Glycine
  • Hydrogen Sulfide