Badr M Z, Chen T S
Drug Nutr Interact. 1987;5(1):43-7.
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.
研究了给予葡萄糖对甲氨蝶呤诱导的小鼠体重减轻和胃肠道毒性的影响。采用外翻肠囊技术，D - 葡萄糖和L - 酪氨酸的转运对照速率（μmol/g/hr）分别为35.0和10.0。在用甲氨蝶呤预处理的动物（腹腔注射25mg/kg/天，共4天）中，这些速率分别降至10.9和6.3μmol/g/hr。然而，当将未处理小鼠的肠囊暴露于甲氨蝶呤（10⁻³M）时，该药物对D - 葡萄糖或L - 酪氨酸的转运速率没有显著影响。甲氨蝶呤体内预处理也导致动物体重下降15%。在甲氨蝶呤给药前1小时给予葡萄糖（0.5/g/kg，腹腔注射）可防止葡萄糖和酪氨酸的跨粘膜转运受到抑制。葡萄糖还减轻了甲氨蝶呤引起的体重减轻。用不可代谢的糖3 - O - 甲基葡萄糖进行类似处理对甲氨蝶呤诱导的毒性没有显著影响。数据表明，葡萄糖与甲氨蝶呤联合给药可能具有潜在的临床价值，因为葡萄糖可能减轻接受该药物治疗的患者中甲氨蝶呤的毒性作用。
