Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors

Vicki Klimberg, Alex A. Pappas, Emmanuel Nwokedi, Joseph C. Jensen, J. Ralph Broadwater, Nicholas P. Lang, Kent C. Westbrook

Research output: Contribution to journalArticle

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Abstract

This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (−GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0±0.20 nmol/g for the +GLN group vs 28.8±0.10 nmol/g for the −GLN group and 35.6±0.18 nmol/g for the +GLN group vs 32.5±0.16 nmol/g for the −GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147±0.007 μm/L for the +GLN group vs 0.120±0.006 μm/L for the −GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (−2.41±1.3 cm3 for the +GLN group vs −0.016±0.9 cm3 for the −GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 ±0.13 μmol/g per hour for the +GLN group vs 1.47±0.22 μmol/g per hour for the −GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.

Original languageEnglish (US)
Pages (from-to)1317-1320
Number of pages4
JournalArchives of Surgery
Volume127
Issue number11
DOIs
StatePublished - 1992
Externally publishedYes

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Glutamine
Methotrexate
Neoplasms
Diet
Glutaminase
Random Allocation
Tumor Burden
Intraperitoneal Injections
Sarcoma

ASJC Scopus subject areas

  • Surgery

Cite this

Klimberg, V., Pappas, A. A., Nwokedi, E., Jensen, J. C., Broadwater, J. R., Lang, N. P., & Westbrook, K. C. (1992). Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors. Archives of Surgery, 127(11), 1317-1320. https://doi.org/10.1001/archsurg.1992.01420110063013

Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors. / Klimberg, Vicki; Pappas, Alex A.; Nwokedi, Emmanuel; Jensen, Joseph C.; Broadwater, J. Ralph; Lang, Nicholas P.; Westbrook, Kent C.

In: Archives of Surgery, Vol. 127, No. 11, 1992, p. 1317-1320.

Research output: Contribution to journalArticle

Klimberg, V, Pappas, AA, Nwokedi, E, Jensen, JC, Broadwater, JR, Lang, NP & Westbrook, KC 1992, 'Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors', Archives of Surgery, vol. 127, no. 11, pp. 1317-1320. https://doi.org/10.1001/archsurg.1992.01420110063013
Klimberg, Vicki ; Pappas, Alex A. ; Nwokedi, Emmanuel ; Jensen, Joseph C. ; Broadwater, J. Ralph ; Lang, Nicholas P. ; Westbrook, Kent C. / Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors. In: Archives of Surgery. 1992 ; Vol. 127, No. 11. pp. 1317-1320.
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abstract = "This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (−GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0±0.20 nmol/g for the +GLN group vs 28.8±0.10 nmol/g for the −GLN group and 35.6±0.18 nmol/g for the +GLN group vs 32.5±0.16 nmol/g for the −GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147±0.007 μm/L for the +GLN group vs 0.120±0.006 μm/L for the −GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (−2.41±1.3 cm3 for the +GLN group vs −0.016±0.9 cm3 for the −GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 ±0.13 μmol/g per hour for the +GLN group vs 1.47±0.22 μmol/g per hour for the −GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.",
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