Effect of Glutamine Supplementation on Protein Metabolism and Glutathione in Tumor-Bearing Rats
Summary: Tumor development led to a significant weight loss, but this weight loss was significantly lessened by glutamine supplementation because of an increase in muscle protein synthesis.
Abstract
Background: Since tumor-bearing rats are deficient in glutamine, we investigated whether (1) glutamine and glutathione deficiency occur in tumor-bearing rats, (2) glutamine supplementation caused an increase of glutathione levels in host tissues and tumor, (3) glutamine enhances protein synthesis in host tissues, and (4) glutamine stimulated the tumor to synthesize protein and DNA.
Methods: Male Donryu rats were randomized into four groups: (1) non-tumor-bearing rat (NTB) + standard total parenteral nutrition (STPN); (2) NTB + glutamine-supplemented TPN (GTPN); (3) tumor-bearing rat (TB) + STPN; (4) TB + GTPN. On day 0 AH109A rat hepatoma cells were subcutaneously injected into the backs of rats to induce tumor. The animals were maintained on TPN for 6 days from day 10 through day 15. On day 15, 1-14C-leucine was given by a 5-hour continuous infusion (2.0 microCi/h per rat) to determine the fractional synthesis rate and endogenous leucine production. The levels of glutamine and glutathione were measured by HPLC. the tumor DNA synthesis was estimated by bromodeoxyuridine labeling index.
Results: Tumor development led to a significant weight loss, but this weight loss was significantly lessened by glutamine supplementation because of an increase in muscle protein synthesis. Glutamine did not enhance tumor weight, protein, and DNA synthesis in the tumor. Tumor development caused a significant reduction of glutathione in the muscle, jejunum, and liver, but supplemented glutamine increased the levels of glutathione in the jejunum.
Conclusion: Glutamine supplementation is beneficial in preventing deficiencies of glutamine and glutathione and in improving protein metabolism in tumor-bearing rats.