title: The anti-inflammatory effects of methane.
abstract: OBJECTIVE
  Gastrointestinal methane generation has been demonstrated in various stress conditions, but it is not known whether nonasphyxiating amounts have any impact on the mammalian pathophysiology. We set out to characterize the effects of exogenous methane administration on the process of inflammatory events arising after reoxygenation in a large animal model of ischemia-reperfusion.
  
  
  METHODS
  A randomized, controlled in vivo animal study.
  
  
  METHODS
  A university research laboratory.
  
  
  METHODS
  Inbred beagle dogs (12.7 6 2 kg).
  
  
  METHODS
  Sodium pentobarbital-anesthetized animals were randomly assigned to sham-operated or ischemia-reperfusion groups, where superior mesenteric artery occlusion was maintained for 1 hr and the subsequent reperfusion was monitored for 3 hrs. For 5 mins before reperfusion, the animals were mechanically ventilated with normoxic artificial air with or without 2.5% methane. Biological responses to methane-oxygen respirations were defined in pilot rat studies and assay systems were used with xanthine oxidase and activated canine granulocytes to test the in vitro bioactivity potential of different gas concentrations.
  
  
  RESULTS
  The macrohemodynamics and small intestinal pCO(2) gap changes were recorded and peripheral blood samples were taken for plasma nitrite/nitrate and myeloperoxidase analyses. Tissue superoxide and nitrotyrosine levels and myeloperoxidase activity changes were determined in intestinal biopsy samples; structural mucosal damage was measured by hematoxylin and eosin staining. Methane inhalation did not influence the macrohemodynamics but significantly reduced the magnitude of the tissue damage and the intestinal pCO(2) gap changes after reperfusion. Furthermore, the plasma and mucosal myeloperoxidase activity and the intestinal superoxide and nitrotyrosine levels were reduced, whereas the plasma nitrite/nitrate concentrations were increased. Additionally, methane effectively and specifically inhibited leukocyte activation in vitro.
  
  
  CONCLUSIONS
  These data demonstrate the anti-inflammatory profile of methane. The study provides evidence that exogenous methane modulates leukocyte activation and affects key events of ischemia-reperfusion-induced oxidative and nitrosative stress and is therefore of potential therapeutic interest in inflammatory pathologies.
authors.affiliation: Institute of Surgical Research, Department of Biochemistry, University of Szeged, Szeged, Hungary. boros@expsur.szote.u-szeged.hu
authors.forename: Mihály
authors.initials: M
authors.lastname: Boros
authors.forename: Miklós
authors.initials: M
authors.lastname: Ghyczy
authors.forename: Dániel
authors.initials: D
authors.lastname: Érces
authors.forename: Gabriella
authors.initials: G
authors.lastname: Varga
authors.forename: Tünde
authors.initials: T
authors.lastname: Tőkés
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kupai
authors.forename: Csilla
authors.initials: C
authors.lastname: Torday
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D004285:Dogs; D006098:Granulocytes / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D007410:Intestinal Diseases / Q000188:drug therapy / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008297:Male; D008697:Methane / Q000008:administration & dosage / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D008697:Methane