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

Clin Nutr. 2009 Jun;28(3):331-7. doi: 10.1016/j.clnu.2009.02.011. Epub 2009 Mar 26.

Abstract

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 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dipeptides
  • Disease Models, Animal
  • Drug Combinations
  • Glutamine / pharmacology*
  • Glutathione / analysis
  • Glutathione / metabolism
  • Liver / blood supply*
  • Liver / drug effects
  • Liver / injuries
  • Liver / metabolism
  • Male
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha-Tocopherol / pharmacology*

Substances

  • Dipeptides
  • Drug Combinations
  • Tumor Necrosis Factor-alpha
  • Glutamine
  • Nitric Oxide
  • Glutathione
  • alpha-Tocopherol
  • alanylglutamine