Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum.

Junmin Chen,Qiang Sun ,Jing Zhao,Xiaopeng Wang,Lingfeng Yang ,Na Liu,Linjing Wang,Yanying Zhao,Jianbin He ,Lei Chen

doi:10.31083/j.jin.2019.03.174

Abstract

Rats were divided into six groups: sham/control , Dl-3-n-butylphthalide, P1 (low phenytoin, 100 mg/kg), P2 (high phenytoin, 200 mg/kg), NP1 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 100 mg/kg), NP2 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 200 mg/kg). Hematoxylin/eosin and Nissl staining showed that, compared to the sham/control group, the Dl-3-n-butylphthalide group had no obvious hippocampal and cerebellar neuron loss, but there was a significant neuron loss in the P1 and P2 groups (P < 0.05), which was more obvious in the P2 group (P < 0.05). The positive expression of Bax and Bcl-2 proteins in hippocampal and cerebellar neurons was not significantly different between sham and Dl-3-n-butylphthalide groups; however, compared to sham, Bax expression was significantly increased and Bcl-2 was significantly decreased in the hippocampal and cerebellar neurons of rats in both P1 and P2 groups (P < 0.05), being more obvious in the P2 group (P < 0.05). Furthermore, the administration of Dl-3-n-butylphthalide attenuated the deleterious effects of phenytoin (P < 0.05). Our results indicate that phenytoin causes apoptosis of hippocampal and cerebellar neurons in rats in a dose-dependent manner, with the effect of a higher dose being more obvious, whereas, Dl-3-n-butylphthalide inhibits the phenytoin-induced apoptosis of neurons and has a neuroprotective role.

Highlights

Abnormal discharge of the brain, thalamic cortical system, and upper midbrain neurons is the root cause of epilepsy, but its specific pathogenesis remains unclear (Baldassari et al, 2019; Devinsky et al, 2013).Studies have shown that neuronal apoptosis is a key event in the pathogenesis of epilepsy and can play a role in reducing brain damage after epilepsy by inhibiting apoptosis (Dai et al, 2018; Singh et al, 2019).Phenytoin (PHT) is a common antiepileptic drug with a narrow therapeutic spectrum
hematoxylin and eosin (H&E) staining showed no obvious pathological changes in cerebellar neurons in the NBP group compared with sham: cell structure was clear, and the cellular arrangement was organized
Antiepileptic drugs for the treatment of seizures are accompanied by adverse effects, such as cognitive impairment, microcephaly, and congenital disabilities

Summary

Introduction

Abnormal discharge of the brain, thalamic cortical system, and upper midbrain neurons is the root cause of epilepsy, but its specific pathogenesis remains unclear (Baldassari et al, 2019; Devinsky et al, 2013).Studies have shown that neuronal apoptosis is a key event in the pathogenesis of epilepsy and can play a role in reducing brain damage after epilepsy by inhibiting apoptosis (Dai et al, 2018; Singh et al, 2019).Phenytoin (PHT) is a common antiepileptic drug with a narrow therapeutic spectrum. Abnormal discharge of the brain, thalamic cortical system, and upper midbrain neurons is the root cause of epilepsy, but its specific pathogenesis remains unclear (Baldassari et al, 2019; Devinsky et al, 2013). Studies have shown that neuronal apoptosis is a key event in the pathogenesis of epilepsy and can play a role in reducing brain damage after epilepsy by inhibiting apoptosis (Dai et al, 2018; Singh et al, 2019). Numerous studies have shown that PHT has antiepileptic properties and may induce neuronal apoptosis and damage the nervous system (Kaushal et al, 2016). Preventing neuronal apoptosis is essential for the treatment of epilepsy

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Conclusion