Eur Rev Med Pharmacol Sci 2018; 22 (1): 250-261
DOI: 10.26355/eurrev_201801_14126

Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats

Y. Song, M. Zhong, F.-C. Cai

Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, China. weeliched@hainan.net


OBJECTIVE: Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats.

MATERIALS AND METHODS: Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression.

RESULTS: OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (p<0.05). OXC administration causes histological changes of neurocytes. OXC 281.25 mg/kg or more concentration significantly decreased neurocytes counts and increased TUNEL-staining positive neurocytes compared to Control group (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased caspase 3 activity compared to Control group in P5 rats (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased Bax, Bax/Bcl-2 ratio and cytochrome C release in frontal lobes compared to Control group in P5 rats (p<0.05).

CONCLUSIONS: Oxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

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To cite this article

Y. Song, M. Zhong, F.-C. Cai
Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats

Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 1
Pages: 250-261
DOI: 10.26355/eurrev_201801_14126