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Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells

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Title: Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells
Authors: Kurosawa, Yuko Browse this author
Furugen, Ayako Browse this author →KAKEN DB
Nishimura, Ayako Browse this author
Narumi, Katsuya Browse this author
Kobayashi, Masaki Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Keywords: Antiepileptic drug
Folic acid
Placenta
Folate receptor-alpha
Reduced folate carrier
Proton-coupled folate transporter
Issue Date: Apr-2018
Publisher: Elsevier
Journal Title: Toxicology in vitro
Volume: 48
Start Page: 104
End Page: 110
Publisher DOI: 10.1016/j.tiv.2017.12.003
Abstract: 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.
Rights: ©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/73802
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 古堅 彩子

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