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

Background: Hydrogen sulfide (H2S) 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 H2S 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 2 h 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 H2S (both P<0.05) than non-diabetics when they underwent MIR. MIR significantly increased the serum level of H2S (49.5 +/- 7.1 mu M), H2S-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 mu M, 0.15 +/- 0.4 nmol/mg and 1.2 +/- 0.4%, respectively). Administration of NaHS increased the H2S level (65.8 +/- 6.9 mu M) and had little effect on H2S production activity (6.5 +/- 2.2 nmol/mg), while PAG reduced both the H2S level (29.2 +/- 5.0 mu M) and H2S-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-alpha, 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 H2S may play a protective role in MIR-induced myocardial injury in diabetics by its anti-apoptotic, anti-oxidative and anti-inflammatory activities. (C) 2011 Published by Elsevier Ireland Ltd.