Effect of supplemental dietary glutamine on methotrexate concentrations in tumors.
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.
Klimberg
V S
VS
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205.
Pappas
A A
AA
Nwokedi
E
E
Jensen
J C
JC
Broadwater
J R
JR
Lang
N P
NP
Westbrook
K C
KC
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D002149:Energy Intake; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000737:chemistry / Q000178:diet therapy* / Q000188:drug therapy
D005973:Glutamine; D008727:Methotrexate