title: Inhaled Methane Limits the Mitochondrial Electron Transport Chain Dysfunction during Experimental Liver Ischemia-Reperfusion Injury.
abstract: BACKGROUND
  Methanogenesis can indicate the fermentation activity of the gastrointestinal anaerobic flora. Methane also has a demonstrated anti-inflammatory potential. We hypothesized that enriched methane inhalation can influence the respiratory activity of the liver mitochondria after an ischemia-reperfusion (IR) challenge.
  
  
  METHODS
  The activity of oxidative phosphorylation system complexes was determined after in vitro methane treatment of intact liver mitochondria. Anesthetized Sprague-Dawley rats subjected to standardized 60-min warm hepatic ischemia inhaled normoxic air (n = 6) or normoxic air containing 2.2% methane, from 50 min of ischemia and throughout the 60-min reperfusion period (n = 6). Measurement data were compared with those on sham-operated animals (n = 6 each). Liver biopsy samples were subjected to high-resolution respirometry; whole-blood superoxide and hydrogen peroxide production was measured; hepatocyte apoptosis was detected with TUNEL staining and in vivo fluorescence laser scanning microscopy.
  
  
  RESULTS
  Significantly decreased complex II-linked basal respiration was found in the normoxic IR group at 55 min of ischemia and a lower respiratory capacity (~60%) and after 5 min of reperfusion. Methane inhalation preserved the maximal respiratory capacity at 55 min of ischemia and significantly improved the basal respiration during the first 30 min of reperfusion. The IR-induced cytochrome c activity, reactive oxygen species (ROS) production and hepatocyte apoptosis were also significantly reduced.
  
  
  CONCLUSIONS
  The normoxic IR injury was accompanied by significant functional damage of the inner mitochondrial membrane, increased cytochrome c activity, enhanced ROS production and apoptosis. An elevated methane intake confers significant protection against mitochondrial dysfunction and reduces the oxidative damage of the hepatocytes.
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Gerda
authors.initials: G
authors.lastname: Strifler
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Tuboly
authors.affiliation: Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Szél
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Enikő
authors.initials: E
authors.lastname: Kaszonyi
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Chun
authors.initials: C
authors.lastname: Cao
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Mészáros
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Boros
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Petra
authors.initials: P
authors.lastname: Hartmann
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008697:Methane / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D013481:Superoxides; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D008697:Methane