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Effect of supplemental dietary glutamine on methotrexate concentrations in tumors
V S Klimberg1, A A Pappas, E Nwokedi
1Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205.
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 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.
Insights
Supplemental dietary glutamine (GLN) increased methotrexate concentrations in sarcoma tumors and serum of rats. This suggests glutamine may offer therapeutic benefits in cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Nutritional Science
Background:
- Methotrexate is a common chemotherapy agent.
- Dietary glutamine (GLN) plays a role in cellular metabolism and immune function.
- Understanding nutrient-drug interactions is crucial for optimizing cancer therapy.
Purpose of the Study:
- To investigate the impact of supplemental dietary glutamine on methotrexate pharmacokinetics in sarcoma-bearing rats.
- To determine if glutamine affects methotrexate concentrations in tumor tissue and serum.
- To assess the influence of glutamine on tumor response and glutaminase activity.
Main Methods:
- Rats with sarcoma were randomized to receive either a glutamine-supplemented diet (+GLN) or a standard diet (-GLN).
- All rats received an intraperitoneal injection of methotrexate sodium (20 mg/kg).
- Methotrexate concentrations in tumor and serum were measured at 24 and 48 hours; tumor volume and glutaminase activity were also assessed.
Main Results:
- Supplemental GLN significantly increased methotrexate concentrations in tumor tissues at 24 and 48 hours.
- Arterial methotrexate levels were elevated in the +GLN group at 48 hours.
- Greater tumor volume loss was observed in the +GLN group even at 24 hours, with suppressed glutaminase activity.
- Tumor morphometrics did not differ between groups.
Conclusions:
- Supplemental dietary glutamine enhances tumor methotrexate concentrations and promotes tumor volume reduction in this sarcoma model.
- Glutamine may exert therapeutic effects beyond nutrition in cancer patients undergoing methotrexate therapy.
- Further research is warranted to explore glutamine's role in optimizing chemotherapy efficacy.