Anti-apoptotic and anti-inflammatory effects of hydrogen sulfide in a rat model of regional myocardial l/R

Ahila Sivarajah, Massimo Collino, Mohammed Yasin, Elisa Benetti, Margherita Gallicchio, Emanuela Mazzon, Salvatore Cuzzocrea, Roberto Fantozzi, Christoph Thiemermann

Research output: Contribution to journalArticlepeer-review

Abstract

Hydrogen sulfide (H 2S) is a novel gaseous mediator produced by cystathionine-β-synthase and cystathionines-α-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H 2S donor (sodium hydrogen sulfide [NaHS]) on the infarct size and apoptosis caused by ischemia (25 min) and reperfusion (2 h). Furthermore, we investigated the potential mech-anism(s) of the cardioprotective effect(s) afforded by NaHS. Specifically, we demonstrate that NaHS (1) attenuates the increase in caspase 9 activity observed in cardiac myocytes isolated from the area at risk (AAR) of hearts subjected in vivo to regional myocardial l/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial l/R. The cardioprotective effects of NaHS were abolished by 5-hydroxydeconoate, a putative mitochondrial adenosine triphosphate-sensitive potassium channel blocker. Furthermore, NaHS attenuated the increase in the l/R-induced (1) phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase, (2) translocation from the cytosol to the nucleus of the p65 subunit of nuclear factor-kb, (3) intercellular adhesion molecule 1 expression, (4) polymorphonuclear leukocyte accumulation, (5) myeloperoxidase activity, (6) malondialdehyde levels, and (7) nitrotyrosine staining determined in the AAR obtained from rat hearts subjected to regional myocardial l/R. In conclusion, we demonstrate that the cardioprotective effect of NaHS is secondary to a combination of antiapoptotic and anti-inflammatory effects. The antiapoptotic effect of NaHS may be in part due to the opening of the putative mitochondrial adenosine triphosphate-sensitive potassium channels.

Original languageEnglish
Pages (from-to)267-274
Number of pages8
JournalShock
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2009

Keywords

  • Apoptosis
  • Hydrogen sulfide
  • Infarct size
  • Inflammation and regional myocardial infarction

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine
  • Medicine(all)

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