Alanyl-glutamine preserves hepatic glutathione stores after 5-FU treatment

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. 5-fluorouracil (5-FU) considered the most active antineoplastic agent in the treatment of advanced gastrointestinal malignancies, causes hepatic GSH depletion. Glutamine (GLN) augments host defenses and may be important in GSH synthesis. We hypothesized that alanyl-glutamine (ALA-GLN) may protect liver cells from oxidant injury, like GLN, by increasing hepatic GSH stores. Two rat groups received standard parenteral nutrition (STD) supplemented with or without ALA-GLN for 7 days. After the antineoplastic agent 5-FU was injected, the concentration measurements were significantly different in ALA-GLN group compared with STD animals for serum GLN (687.3 +/- 49.8 vs. 504.9 +/- 38.6 uMol/L, P < 0.05), serum GSH (14.37 +/- 5.16 vs. 7.08 +/- 3.16 uMol/L, P < 0.01) and in liver GSH content (6.86 +/-2.46 vs. 4.38 +/-1.63 uMol/g liver tissue, P < 0.05). Rats in ALA-GLN group had lower elevations in hepatic enzymes induced by 5-FU. The experiment demonstrated that the supplemented nutrition ALA-GLN, like glutamine, protected the liver function and improved survival during 5-FU treatment by increasing GSH biosynthesis and by preserving the GSH stores of hepatic tissue.