Prevention of methotrexate-induced gastrointestinal toxicity by glucose

The effect of administration of glucose on methotrexate-induced body weight loss and gastrointestinal toxicity in mice was investigated. Using the everted sac technique, control rates (mumol/g/hr) of transport of D-glucose and L-tyrosine were 35.0 and 10.0, respectively. In animals pretreated with methotrexate (25 mg/kg/day i.p. for 4 days), these rates decreased to 10.9 and 6.3 mumol/g/hr, respectively. However, when intestinal sacs from untreated mice were exposed to MTX (10(-3) M), the drug had no significant effect on rates of transport of D-glucose or L-tyrosine. Methotrexate pretreatment in vivo also caused a 15% loss in animal body weights. Administration of glucose (0.5/g/kg. i/p.) 1 hour prior to methotrexate prevented the inhibition of transmucosal transport of both glucose and tyrosine. Glucose also reduced the body weight loss caused by methotrexate. Similar treatment with the nonmetabolizable sugar, 3-O-methylglucose, had no significant effect on the methotrexate-induced toxicity. The data suggest that coadministration of glucose with methotrexate may have a potential clinical value, since glucose may alleviate the toxic effects of methotrexate in patients receiving this drug.