nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2017-1S-89-96nnp-734Research ArticleREVIEWSОБЗОРЫMechanisms of valproate-induced teratogenesisМеханизмы вальпроат-индуцированного тератогенезаДмитренкоД. В.DmitrenkoD. V.

660022 Красноярск, ул. Партизана Железняка, 1

1, Partisan Zheleznyak St., Krasnoyarsk 660022

ШнайдерН. А.ShnaiderN. A.

660022 Красноярск, ул. Партизана Железняка, 1

1, Partisan Zheleznyak St., Krasnoyarsk 660022

СтроцкаяИ. Г.StrotskayaI. G.

660022 Красноярск, ул. Партизана Железняка, 1

1, Partisan Zheleznyak St., Krasnoyarsk 660022

КичкайлоА. С.KichkayloA. S.

660022 Красноярск, ул. Партизана Железняка, 1

1, Partisan Zheleznyak St., Krasnoyarsk 660022

ЗобоваС. Н.ZobovaS. N.

660022 Красноярск, ул. Партизана Железняка, 1;

660036 Красноярск, ул. Академгородок, 50

1, Partisan Zheleznyak St., Krasnoyarsk 660022;

50, Akademgorodok St., Krasnoyarsk 660036

ФГБОУ ВО «Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого» Минздрава РоссииРоссияProfessor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of RussiaRussian FederationФГБОУ ВО «Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого» Минздрава России; ФГБНУ «Федеральный исследовательский центр “Красноярский научный центр Сибирского отделения Российской академии наук”»РоссияProfessor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia; Krasnoyarsk Research Center, Siberian Branch, Russian Academy of SciencesRussian Federation20171406201791SSPECIAL ISSUE: EPILEPSY8996Copyright © Dmitrenko D.V., Shnaider N.A., Strotskaya I.G., Kichkaylo A.S., Zobova S.N., 20172017Дмитренко Д.В., Шнайдер Н.А., Строцкая И.Г., Кичкайло А.С., Зобова С.Н.Dmitrenko D.V., Shnaider N.A., Strotskaya I.G., Kichkaylo A.S., Zobova S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/734

The risks associated with in utero antiepileptic drug (AED) exposure are of great importance for both epileptic women and their offspring. This review considers the basic mechanisms of valproate-induced teratogenesis. It discusses the mechanisms of fetal valproic acid accumulation, oxidative stress, folate antagonism, and histone deacetylase inhibition. Analysis of the literature has shown a large number of studies that prove and disprove different mechanisms of valproate-induced teratogenesis. Histone deacetylase inhibition and oxidative stress have the most pronounced teratogenic effect; moreover, both mechanisms are particularly important in the first trimester of pregnancy when DNA dysregulation has the greatest impact on organogenesis. All the described mechanisms (and possibly many others) along with individual genetic characteristics, environmental factors, and lifestyle, each of which has not been defined, may lead to an increased risk for the teratogenic effects of valproic acid.

Риски, связанные с внутриутробным влиянием противоэпилептических препаратов (ПЭП), имеют большое значение как для женщин, страдающих эпилепсией, так и для их потомства. В данном обзоре рассмотрены основные механизмы вальпроат-индуцированного тератогенеза. Обсуждаются механизмы накопления вальпроевой кислоты внутри плода, окислительный стресс, антагонизм фолатов и ингибирование гистондеацетилазы. Анализ литературы выявил большое количество исследований, доказывающих и опровергающих различные механизмы вальпроат-индуцированного тератогенеза. Ингибирование гистондеацетилазы и окислительный стресс обладают наиболее выраженным тератогенным влиянием; при этом оба механизма особенно значимы в I триместре беременности, когда дисрегуляция ДНК имеет наибольшее влияние на органогенез. Все описанные механизмы (и, возможно, многие другие), наряду с индивидуальными генетическими особенностями, факторами окружающей среды и образа жизни, каждый из которых не определен, могут привести к повышенному риску тератогенных эффектов вальпроевой кислоты.

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The authors declare that there are no conflicts of interest present.