{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T23:07:27Z","timestamp":1776294447365,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,5,29]],"date-time":"2015-05-29T00:00:00Z","timestamp":1432857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Commission FP7-PEOPLE-2011-CIG","award":["293800"],"award-info":[{"award-number":["293800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Antiepileptic drugs (<jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s) affect the expression of carriers for drugs and nutrients at several blood\u2010tissue barriers, but their impact on placental carriers is largely unknown. Our aim was to study the effects of <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s in human placental cells on the expression of carriers for hormones, nutrients, and drugs: folate placental uptake carriers (reduced folate carrier, <jats:styled-content style=\"fixed-case\">RFC<\/jats:styled-content>; folate receptor \u03b1, <jats:styled-content style=\"fixed-case\">FR<\/jats:styled-content>\u03b1) and efflux transporters (breast cancer resistance protein, <jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content> and multidrug resistance protein 2) and thyroid hormone uptake transporters (<jats:sc>l<\/jats:sc>\u2010type amino acid transporter\u2010<jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content>1 and organic anion transporting polypeptides\u2010<jats:styled-content style=\"fixed-case\">OATP<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The human trophoblast BeWo cells were incubated with phenytoin (<jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>), valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>), carbamazepine (<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>), levetiracetam (<jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content>), lamotrigine (<jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content>), or their vehicles at concentrations that mostly represent their therapeutic range. <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and western blot analysis were utilized to study the effects of <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s on carriers\u2019 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression, respectively. The activity of <jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content> was evaluated by accumulation studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with controls, <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010treated cells displayed half the levels of <jats:styled-content style=\"fixed-case\">RFC mRNA<\/jats:styled-content> and protein (p\u00a0&lt;\u00a00.05) and up to 2.7\u2010fold increases in <jats:styled-content style=\"fixed-case\">BCRP mRNA<\/jats:styled-content> and protein expression (p\u00a0&lt;\u00a00.05), together with enhanced <jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content> activity. <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> increased the expression of <jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content>1 by 2.9\u2010fold and 2.5\u2010fold, respectively (p\u00a0&lt;\u00a00.01). <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> modulated the levels of <jats:styled-content style=\"fixed-case\">FR<\/jats:styled-content>\u03b1 transcript and protein, whereas <jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content> altered those of <jats:styled-content style=\"fixed-case\">RFC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> LAT<\/jats:styled-content>1, and <jats:styled-content style=\"fixed-case\">OATP<\/jats:styled-content>s 1A2 and 4A1. <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> affected carrier expression at the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> but not the protein level. All the <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s altered to a modest extent the transcription of nuclear receptors known to regulate transporter expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These findings suggest a possible effect of <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s on placental transport mechanisms for folate and thyroid hormones as well as those involved in the elimination of potential toxins from the fetus. Identification of <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content> effects on the placental barrier could be a first step toward a more rational pharmacotherapy and supplemental therapy in pregnant women with epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13037","type":"journal-article","created":{"date-parts":[[2015,5,29]],"date-time":"2015-05-29T18:45:16Z","timestamp":1432925116000},"page":"1023-1032","source":"Crossref","is-referenced-by-count":51,"title":["Antiepileptic drugs alter the expression of placental carriers: An in\u00a0vitro study in a human placental cell line"],"prefix":"10.1111","volume":"56","author":[{"given":"Miriam","family":"Rubinchik\u2010Stern","sequence":"first","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miri","family":"Shmuel","sequence":"additional","affiliation":[{"name":"Institute for Drug Research 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