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Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors
V. Suzanne Klimberg, MD;
Alex A. Pappas, MD;
Emmanuel Nwokedi;
Joseph C. Jensen, MD;
J. Ralph Broadwater, MD;
Nicholas P. Lang, MD;
Kent C. Westbrook, MD
Arch Surg. 1992;127(11):1317-1320.
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.
(Arch Surg. 1992;127:1317-1320)
Author Affiliations
From the Department of Surgery, University of Arkansas for Medical Sciences, Little Rock.
Footnotes
Accepted for publication July 25, 1992.
Presented at the 45th Annual Cancer Symposium of the Society of Surgical Oncology, New York, NY, March 16, 1992.
Reprint requests to Department of Surgery, University of Arkansas for Medical Sciences, 4301 W Markham, Slot 725, Little Rock, AR 72205 (Dr Klimberg).
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