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

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.

• Authors: Hemant Sheth, Tariq Hafez, George K Glantzounis, Alexander M Seifalian, Barry Fuller, Brian R Davidson
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 26 Issue 1 Pg. 194-200 (Jan 2011) ISSN: 1440-1746 [Electronic] Australia
• PMID: 21175814 (Publication Type: Journal Article)
• Copyright: © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Chemical References

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

Topics

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