Carl G F, Smith M L
Medical Research, VA Medical Center, Augusta, Georgia 30910.
Epilepsia. 1992 Mar-Apr;33(2):372-5. doi: 10.1111/j.1528-1157.1992.tb02330.x.
Chronic phenytoin (PHT) treatment has long been associated with folate deficiency. It has been suggested that pH changes in the gut associated with PHT ingestion may be responsible for decreased folate uptake either by direct inhibition of folate transport into the intestinal mucosa or by inhibition of folate conjugase activity. To examine these possibilities, rats were gavaged chronically with PHT using either the sodium salt (NaPHT) or the free acid (HPHT) in the presence of folic acid as the dietary source of folate. The NaPHT caused a greater depletion of folate in the liver and brain and a significant increase in methylenetetrahydrofolate reductase activity in the liver. The HPHT caused a significantly decreased weight gain over the 8 weeks of treatment and resulted in a much higher liver PHT concentration and a slightly lower plasma PHT concentration. These data support the hypothesis that PHT-induced changes in pH in the gut affect the enterohepatic circulation of folate.
长期以来，苯妥英（PHT）慢性治疗一直与叶酸缺乏有关。有人提出，与摄入PHT相关的肠道pH值变化可能是叶酸摄取减少的原因，这可能是通过直接抑制叶酸转运进入肠黏膜，或通过抑制叶酸结合酶活性来实现的。为了检验这些可能性，在以叶酸作为膳食叶酸来源的情况下，用苯妥英钠（NaPHT）或游离酸（HPHT）对大鼠进行长期灌胃。NaPHT导致肝脏和大脑中的叶酸消耗更大，并且肝脏中的亚甲基四氢叶酸还原酶活性显著增加。HPHT在8周的治疗期间导致体重增加显著减少，并导致肝脏中PHT浓度更高，血浆PHT浓度略低。这些数据支持了以下假设：PHT引起的肠道pH值变化会影响叶酸的肠肝循环。
