title: L-α-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats.
abstract: BACKGROUND
  We set out to investigate the microcirculatory consequences of hepatic ischemia-reperfusion (IR) injury and the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated phospholipid derivative, on postischemic hepatocellular damage, with special emphasis on the expression of nicotinamide adenine dinucleotide phosphate oxidase type 4 (NOX4), which is predominantly expressed in hepatic microvessels.
  
  
  METHODS
  Anesthetized male Sprague-Dawley rats were subjected to 60-min ischemia of the left liver lobes and 180-min reperfusion, with or without GPC treatment (50 mg/kg intravenously 5 min before reperfusion, n = 6 each). A third group (n = 6) served as saline-treated control. Noninvasive online examination of the hepatic microcirculation was performed hourly by means of modified spectrometry. Plasma tumor necrosis factor (TNF-α), high-mobility group box 1 protein (HMGB1), plasma aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels, tissue xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) activities, and expressions of NOX2 and NOX4 proteins were determined.
  
  
  RESULTS
  Liver IR resulted in significant increases in NOX2 and NOX4 expressions and XOR and MPO activities, and approximately 2-fold increases in the levels of the inflammatory cytokines TNF-α and HMGB1. The microvascular blood flow and tissue oxygen saturation decreased by ∼20% from control values. GPC administration ameliorated the postischemic microcirculatory deterioration and reduced the liver necroenzyme levels significantly; the NOX4 expression, MPO activity, and HMGB1 level were also decreased, whereas the NOX2 expression, TNF-α level, and XOR activity were not influenced by GPC pretreatment.
  
  
  CONCLUSIONS
  NOX4 activation is a decisive component in the IR-induced microcirculatory dysfunction. Exogenous GPC ameliorates the inflammatory activation, and preserves the postischemic microvascular perfusion and liver functions, these effects being associated with a reduced hepatic expression of NOX4.
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Petra
authors.initials: P
authors.lastname: Hartmann
authors.affiliation: Institute of Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Aachen, Germany.
authors.forename: Ngwi
authors.initials: N
authors.lastname: Fet
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Garab
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Szabó
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
authors.affiliation: Institute of Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Aachen, Germany.
authors.forename: Pramod Kadaba
authors.initials: PK
authors.lastname: Srinivasan
authors.affiliation: Institute of Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Aachen, Germany.
authors.forename: René H
authors.initials: RH
authors.lastname: Tolba
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary. Electronic address: boros.mihaly@med.szote.u-szeged.hu.
authors.forename: Mihály
authors.initials: M
authors.lastname: Boros
mesh_terms: D000818:Animals; D005997:Glycerylphosphorylcholine / Q000502:physiology / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D014968:Xanthine Dehydrogenase / Q000378:metabolism
chemical_list: D005997:Glycerylphosphorylcholine; D009195:Peroxidase; D014968:Xanthine Dehydrogenase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat
keywords: HMGB1; Ischemia-reperfusion; Liver; Microcirculation; Modified spectrometry; Myeloperoxidase; NOX2; NOX4; TNF-α