Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells
Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells
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DOI：
10.1016/j.tiv.2017.12.003
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发表时间：
2018-04-01
影响因子：
3.2
通讯作者：
Iseki, Ken
中科院分区：
文献类型：
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作者：
Kurosawa, Yuko;Furugen, Ayako;Iseki, Ken
怀孕期间的叶酸状况对胎儿的发育和健康很重要。胎盘在为胎儿提供叶酸方面起着重要作用。大多数癫痫患者在怀孕期间继续服用药物。在本研究中，我们的目的是评估16种抗癫痫药物，临床上用于治疗癫痫，在两个体外胎盘模型，BeWo和JEG-3细胞的叶酸摄取的影响。短期暴露于抗癫痫药物对BeWo细胞摄取[H-3]-叶酸没有影响。然而，长期暴露（24小时）丙戊酸（VPA）增加[H-3]-叶酸摄取BeWo和JEG-3细胞。VPA处理24小时可增加叶酸受体α（FR α）和质子偶联叶酸转运蛋白（PCFT）mRNA的表达;然而，它并不影响叶酸载体表达的减少。这些结果表明，暴露于VPA后叶酸摄取的增加可归因于FR α和PCFT表达的诱导。此外，本研究表明，暴露于临床浓度的奥卡西平和司替戊醇降低了BeWo细胞的活力。因此，本研究的结果可能有助于更好地了解抗癫痫药物的毒性机制，并估计其对胎儿的潜在风险。
Folate status during pregnancy is important for fetal development and health. The placenta plays an important role in supplying the fetus with folate. Most women with epilepsy continue their medication during pregnancy. In the present study, we aimed to evaluate the effects of 16 antiepileptic drugs, clinically used for treatment of epilepsy, on folic acid uptake in two in vitro placental models, BeWo and JEG-3 cells. Short-term exposure to antiepileptic drugs had no effects on [H-3]-folic acid uptake by BeWo cells. However, long-term exposure (24 h) to valproic acid (VPA) increased [H-3]-folic acid uptake by BeWo and JEG-3 cells. VPA treatment for 24 h increased folate receptor-alpha (FR alpha) and proton-coupled folate transporter (PCFT) mRNA expression; however, it did not affect reduced folate carrier expression. These results suggested that the increase in folic acid uptake after exposure to VPA can be attributed to the induction of FR alpha and PCFT expression. Furthermore, the present study showed that exposure to clinical concentrations of oxcarbazepine and stiripentol reduced the viability of BeWo cells. Therefore, the findings of the present study may contribute to better understanding of the mechanisms of toxicity of antiepileptic drugs, and estimation of their potential risk to fetus.