Effect of supplemental dietary glutamine on methotrexate concentrations in tumors
V. S. Klimberg, A. A. Pappas, E. Nwokedi, J. C. Jensen, J. R. Broadwater, N. P. Lang and K. C. Westbrook
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205.
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
microns/L for the +GLN group vs 0.120 +/- 0.006 microns/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 mumol/g per hour for the +GLN
group vs 1.47 +/- 0.22 mumol/g per hour for the -GLN group). This study
suggests that GLN may have therapeutic as well as nutritional benefit in
oncology patients.