title: Glycine maintains mitochondrial activity and bile composition following warm liver ischemia-reperfusion injury.
abstract: OBJECTIVE
  Experimental studies have shown protective effect by the non-essential amino acid glycine to liver ischemia-reperfusion (I/R) injury but the mechanism of action is unknown.
  
  
  METHODS
  A rabbit model of hepatic lobar I/R was used. Three groups of animals (n=6) were studied: Sham group (laparotomy alone), ischemia reperfusion (I/R) group (1 h of liver lobar ischemia and 6 h of reperfusion), and a glycine I/R group (intravenous glycine 5 mg/kg prior to the I/R protocol). Systemic and hepatic hemodynamics, degree of liver injury (bile flow, transaminases), hepatic microcirculation, mitochondrial activity (redox state of cytochrome oxidase), bile composition and cytokines (tumor necrosis factor-α and interleukin-8) were measured during the experiment.
  
  
  RESULTS
  Glycine administration increased portal blood flow, bile production, hepatic microcirculation and maintained cytochrome oxidase activity as compared with the I/R group during reperfusion. Glycine also reduced bile lactate surge and stimulated acetoacetate release in bile during reperfusion versus the I/R group. Cytokine levels (tumor necrosis factor-α, interleukin-8) and hepatocellular injury (aspartate aminotransferase and alanine aminotransferase) were significantly reduced by glycine administration.
  
  
  CONCLUSIONS
  Intravenous glycine administration reduces liver warm I/R injury by reducing the systemic inflammatory response, and maintaining cellular energy production.
authors.affiliation: Hepatopancreatobiliary and Liver Transplant Unit, University Department of Surgery, Royal Free Hospital and Royal Free and University College Medical School, London, UK.
authors.forename: Hemant
authors.initials: H
authors.lastname: Sheth
authors.forename: Tariq
authors.initials: T
authors.lastname: Hafez
authors.forename: George K
authors.initials: GK
authors.lastname: Glantzounis
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.forename: Barry
authors.initials: B
authors.lastname: Fuller
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D016209:Interleukin-8 / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D003576:Electron Transport Complex IV; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005998:Glycine