Glycine maintains mitochondrial activity and bile composition following warm liver ischemia-reperfusion injury

J Gastroenterol Hepatol. 2011 Jan;26(1):194-200. doi: 10.1111/j.1440-1746.2010.06323.x.

Abstract

Background and aim: 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.

Conclusion: Intravenous glycine administration reduces liver warm I/R injury by reducing the systemic inflammatory response, and maintaining cellular energy production.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Bile / metabolism*
  • Disease Models, Animal
  • Electron Transport Complex IV / metabolism
  • Energy Metabolism / drug effects*
  • Glycine / administration & dosage
  • Glycine / pharmacology*
  • Hemodynamics / drug effects
  • Infusions, Intravenous
  • Interleukin-8 / blood
  • Liver / blood supply*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver Circulation / drug effects
  • Microcirculation / drug effects
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Oxidation-Reduction
  • Rabbits
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Warm Ischemia / adverse effects*

Substances

  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Electron Transport Complex IV
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glycine