Glutamine facilitates chemotherapy while reducing toxicity

Vicki Klimberg, E. Nwokedi, L. F. Hutchins, A. A. Pappas, N. P. Lang, J. R. Broadwater, R. C. Read, K. C. Westbrook

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, 'sepsis', and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model.

Original languageEnglish (US)
JournalJournal of Parenteral and Enteral Nutrition
Volume16
Issue number6 SUPPL.
StatePublished - 1992
Externally publishedYes

Fingerprint

methotrexate
Glutamine
glutamine
drug therapy
Methotrexate
glutaminase
Glutaminase
toxicity
Drug Therapy
Tumor Burden
neoplasms
Enterocolitis
enterocolitis
rats
sarcoma
Sarcoma
blood
animal models
diet
granulocyte colony-stimulating factor

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)

Cite this

Klimberg, V., Nwokedi, E., Hutchins, L. F., Pappas, A. A., Lang, N. P., Broadwater, J. R., ... Westbrook, K. C. (1992). Glutamine facilitates chemotherapy while reducing toxicity. Journal of Parenteral and Enteral Nutrition, 16(6 SUPPL.).

Glutamine facilitates chemotherapy while reducing toxicity. / Klimberg, Vicki; Nwokedi, E.; Hutchins, L. F.; Pappas, A. A.; Lang, N. P.; Broadwater, J. R.; Read, R. C.; Westbrook, K. C.

In: Journal of Parenteral and Enteral Nutrition, Vol. 16, No. 6 SUPPL., 1992.

Research output: Contribution to journalArticle

Klimberg, V, Nwokedi, E, Hutchins, LF, Pappas, AA, Lang, NP, Broadwater, JR, Read, RC & Westbrook, KC 1992, 'Glutamine facilitates chemotherapy while reducing toxicity', Journal of Parenteral and Enteral Nutrition, vol. 16, no. 6 SUPPL..
Klimberg V, Nwokedi E, Hutchins LF, Pappas AA, Lang NP, Broadwater JR et al. Glutamine facilitates chemotherapy while reducing toxicity. Journal of Parenteral and Enteral Nutrition. 1992;16(6 SUPPL.).
Klimberg, Vicki ; Nwokedi, E. ; Hutchins, L. F. ; Pappas, A. A. ; Lang, N. P. ; Broadwater, J. R. ; Read, R. C. ; Westbrook, K. C. / Glutamine facilitates chemotherapy while reducing toxicity. In: Journal of Parenteral and Enteral Nutrition. 1992 ; Vol. 16, No. 6 SUPPL.
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