Antiepileptic drugs alter the expression of placental carriers: An in vitro study in a human placental cell line

Summary Objective Antiepileptic drugs (AEDs) affect the expression of carriers for drugs and nutrients at several blood‐tissue barriers, but their impact on placental carriers is largely unknown. Our aim was to study the effects of AEDs in human placental cells on the expression of carriers for horm...

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Bibliographic Details
Published in:Epilepsia (Copenhagen) 2015-07, Vol.56 (7), p.1023-1032
Main Authors: Rubinchik‐Stern, Miriam, Shmuel, Miri, Eyal, Sara
Format: Article
Language:English
Subjects:
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Antiepileptic drugs
ATP Binding Cassette Transporter, Sub-Family G, Member 2
ATP-Binding Cassette Transporters - biosynthesis
Cell Line
Epilepsy - drug therapy
Epilepsy - metabolism
Female
Folate
Gene Expression Regulation, Developmental
Humans
Neoplasm Proteins - biosynthesis
Placenta
Placenta - cytology
Placenta - drug effects
Placenta - metabolism
Pregnancy
Thyroid hormones
Trophoblasts - drug effects
Trophoblasts - metabolism
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Summary:Summary Objective Antiepileptic drugs (AEDs) affect the expression of carriers for drugs and nutrients at several blood‐tissue barriers, but their impact on placental carriers is largely unknown. Our aim was to study the effects of AEDs in human placental cells on the expression of carriers for hormones, nutrients, and drugs: folate placental uptake carriers (reduced folate carrier, RFC; folate receptor α, FRα) and efflux transporters (breast cancer resistance protein, BCRP and multidrug resistance protein 2) and thyroid hormone uptake transporters (l‐type amino acid transporter‐LAT1 and organic anion transporting polypeptides‐OATPs). Methods The human trophoblast BeWo cells were incubated with phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), or their vehicles at concentrations that mostly represent their therapeutic range. RT‐PCR and western blot analysis were utilized to study the effects of AEDs on carriers’ mRNA and protein expression, respectively. The activity of BCRP was evaluated by accumulation studies. Results Compared with controls, VPA‐treated cells displayed half the levels of RFC mRNA and protein (p 
ISSN:0013-9580
1528-1167
DOI:10.1111/epi.13037