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

• Published in: Journal of gastroenterology and hepatology 2011-01, Vol.26 (1), p.194-200
• Main Authors: Sheth, Hemant, Hafez, Tariq, Glantzounis, George K, Seifalian, Alexander M, Fuller, Barry, Davidson, Brian R
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; bile; Bile - metabolism; Biological and medical sciences; Cardiology. Vascular system; Disease Models, Animal; Electron Transport Complex IV - metabolism; Energy Metabolism - drug effects; Gastroenterology. Liver. Pancreas. Abdomen; glycine; Glycine - administration & dosage; Glycine - pharmacology; Hemodynamics - drug effects; hepatic; Infusions, Intravenous; Interleukin-8 - blood; ischemia reperfusion injury; kupffer cells; Liver - blood supply; Liver - drug effects; Liver - metabolism; Liver Circulation - drug effects; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Microcirculation - drug effects; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Other diseases. Semiology; Oxidation-Reduction; Rabbits; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Time Factors; Tumor Necrosis Factor-alpha - blood; Warm Ischemia - adverse effects
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2010.06323.x

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.