Carl G F, Hudson F Z, McGuire B S
Medical Research Service, VA Medical Center, Augusta, GA 30904, USA.
J Nutr. 1997 Nov;127(11):2231-8. doi: 10.1093/jn/127.11.2231.
The anticonvulsant phenytoin causes a decrease in plasma concentrations of folate in epileptic patients. The mechanism underlying this depletion is unknown. To study this mechanism, phenytoin was administered to rats by addition to the diet (3 g phenytoin/kg diet) for up to 8 wk. At selected times during phenytoin administration (0, 3, 7, 10, 14, 28, 42 and 56 d), the composition of the folate pools of intestinal mucosa, liver, bile and brain was determined. The 0-d administration served as the control group. The controls were fed the same diet without phenytoin for the eight weeks of the experiment. Phenytoin administration had minimal effect on either the folate concentration or the composition of the folate pool in intestinal mucosa. Phenytoin administration did, however, cause a depletion of total hepatic folate to about 50% of control, causing the pentaglutamate derivatives of each of the pteridine derivatives to decline rapidly, with the formyl and dihydro derivatives of the pteridine moiety falling more rapidly than the methyl and methylene + tetrahydro derivatives. The monoglutamate of the methylene + unsubstituted tetrahydro derivative increased significantly with time of phenytoin treatment. The mono- and di-glutamate derivatives of the methyltetrahydrofolate increased transiently and significantly in the bile, and the polyglutamate chain length increased significantly in the brain with time of phenytoin treatment. We conclude that phenytoin inhibits the formation of polyglutamyl folates in rat liver.
抗惊厥药物苯妥英会导致癫痫患者血浆中叶酸浓度降低。这种消耗的潜在机制尚不清楚。为了研究该机制，将苯妥英添加到大鼠饮食中（3 g苯妥英/ kg饮食），持续给药8周。在苯妥英给药期间的特定时间点（0、3、7、10、14、28、42和56天），测定肠黏膜、肝脏、胆汁和大脑中叶酸池的组成。0天给药组作为对照组。在实验的八周内，对照组喂食不含苯妥英的相同饮食。苯妥英给药对肠黏膜中叶酸浓度或叶酸池组成的影响最小。然而，苯妥英给药确实导致肝脏总叶酸消耗至对照组的约50%，导致每种蝶啶衍生物的五谷氨酸衍生物迅速下降，蝶啶部分的甲酰基和二氢衍生物下降速度比甲基和亚甲基+四氢衍生物更快。随着苯妥英治疗时间的延长，亚甲基+未取代四氢衍生物的单谷氨酸显著增加。甲基四氢叶酸的单谷氨酸和二谷氨酸衍生物在胆汁中短暂且显著增加，随着苯妥英治疗时间的延长，大脑中的多谷氨酸链长度显著增加。我们得出结论，苯妥英抑制大鼠肝脏中多谷氨酰叶酸的形成。
