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

Abstract

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. 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 microM, Alanyl-Glutamine (AlaGln) 2 mM, or AlaGln 2 mM plus vitamin E 150 microM. Six non-perfused livers were studied in parallel. Liver function, metabolic parameters, oxidative stress and inflammatory parameters have been studied. 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). 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.