Protective effects of glutamine dipeptide and α-tocopherol against ischemia-reperfusion injury in the isolated rat liver

Background & aims: Glutamine and vitamin E may prevent hepatic ischemia-reperfusion (I/R) injuries. Our aim was to investigate the effects of glutamine, either alone or combined with vitamin E, against I/R in the isolated perfused rat liver. Methods: Four groups of 8 livers from male Sprague-Dawley rats were isolated and submitted to a 45-min no-flow ischemia and reperfusion in the presence of alanine 2 mM, alanine 2 mM plus vitamin E 150 mu M, Alanyl-Glutamine (AlaGln) 2 mM, or AlaGln 2 mM plus vitamin E 150 mu M. Six non-perfused livers were studied in parallel. Liver function, metabolic parameters, oxidative stress and inflammatory parameters have been studied. Results: AlaGln was rapidly cleared from the perfusate (436 +/- 41 nmol min(-1) g(-1)) and lowered transaminase release during reperfusion (ALT: -59%), significantly so in the AlaGln + Vit E group (ALT: -65%, p < 0.05). The association of glutamine with vitamin E led to lower degrees NO (-83%, p < 0.05) production, better preserved hepatic glutathione content and, as with vitamin E alone, preserved hepatic vitamin A and significantly decreased malondialdehyde (-85%, p < 0.05). Conclusion: Both glutamine, by attenuating inflammatory response, and vitamin E, via its antioxidative properties, showed complementary protective effects against I/R-induced hepatic injury. These data emphasize the potential benefit of combining glutamine and vitamin E supplementation in hepatic I/R injury. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.