title: Anti-apoptotic and anti-inflammatory effects of hydrogen sulfide in a rat model of regional myocardial I/R.
abstract: Hydrogen sulfide (H2S) is a novel gaseous mediator produced by cystathionine-beta-synthase and cystathionine-gamma-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H2S 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 mechanism(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 I/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial I/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 I/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-kappaB, (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 I/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.
authors.affiliation: Centre for Translational Medicine, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London, UK.
authors.forename: Ahila
authors.initials: A
authors.lastname: Sivarajah
authors.forename: Massimo
authors.initials: M
authors.lastname: Collino
authors.forename: Mohammed
authors.initials: M
authors.lastname: Yasin
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.forename: Margherita
authors.initials: M
authors.lastname: Gallicchio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Roberto
authors.initials: R
authors.lastname: Fantozzi
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiemermann
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003652:Decanoic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004336:Drug Antagonism; D006880:Hydroxy Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D009124:Muscle Proteins; D013440:Sulfides; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C052853:5-hydroxydecanoic acid; C025451:sodium bisulfide