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Mechanisms of valproate-induced teratogenesis

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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.

About the Authors

D. V. Dmitrenko
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022

N. A. Shnaider
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022

I. G. Strotskaya
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022

A. S. Kichkaylo
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
1, Partisan Zheleznyak St., Krasnoyarsk 660022

S. N. Zobova
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia; Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences
Russian Federation

1, Partisan Zheleznyak St., Krasnoyarsk 660022;

50, Akademgorodok St., Krasnoyarsk 660036


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For citation:

Dmitrenko D.V., Shnaider N.A., Strotskaya I.G., Kichkaylo A.S., Zobova S.N. Mechanisms of valproate-induced teratogenesis. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1S):89-96. (In Russ.)

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ISSN 2074-2711 (Print)
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