title: Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine.
abstract: BACKGROUND
  We hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects.
  
  
  METHODS
  Rat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR), with or without GPC administration. The reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed.
  
  
  RESULTS
  GPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers.
  
  
  CONCLUSIONS
  GPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes.
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 Biochemistry, University of Szeged, Szeged, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Görbe
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: Daniella
authors.initials: D
authors.lastname: Pécz
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Petra
authors.initials: P
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D008315:Malondialdehyde; D005997:Glycerylphosphorylcholine; D014968:Xanthine Dehydrogenase; D019255:NADPH Oxidases; D005978:Glutathione; D019803:Glutathione Disulfide