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The neurotoxic effects of prenatal gabapentin and oxcarbazepine exposure on newborn rats.

作者信息

Erisgin Zuleyha, Ayas Bulent, Nyengaard Jens R, Ercument Beyhun N, Terzi Yuksel

机构信息

a Department of Histology and Embryology , Giresun University, Faculty of Medicine , Giresun , Turkey.

b Department of Histology and Embryology , Ondokuz Mayıs University, Faculty of Medicine , Samsun , Turkey.

出版信息

J Matern Fetal Neonatal Med. 2019 Feb;32(3):461-471. doi: 10.1080/14767058.2017.1383378. Epub 2017 Oct 5.

Abstract

AIM

Teratogenicity is a problematic issue for pregnant women because of X-ray radiation, drugs, and genetic and unknown variables. First-generation antiepileptic drugs (AED) like valproic acid are well-known teratogens for developing fetuses. However, their usage is necessary in order to prevent maternal seizures. The underlying mechanism of birth defects associated with AED exposure remains unclear and information about the neurotoxic effects of prenatal exposure to AED is still limited. Oxcarbazepine (OXC) and gabapentin (GBP) are second-generation AED. It still remains unclear how much these drugs are safe during pregnancy. This study aimed to investigate whether any neurotoxic effect of OXC and GBP in utero exposure on the developing brain.

METHODS

Eighteen pregnant Wistar albino rats were divided into six groups. The first group was exposed to OXC at 100 mg/kg/day, the second to GBP at 50 mg/kg/day, and third to saline (0.9% NaCl) at 1.5 ml/day between the first and the fifth days of gestation. The same procedure was applied at the same dosages between the 6th and the 15th days of gestation for the 2nd three groups. Five female offspring (total n = 30, 45 days old) were taken from each group and stereological methods were applied in order to analyze the total and dopaminergic neuron number of the substantia nigra pars compacta (SNc).

CONCLUSION

The result is that the OXC and GBP exposure at different gestational periods may not give rise to congenital malformation and it appears that the GBP exposure during the organogenesis period proliferatively affects the total number of neurons.

摘要

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