INTRODUCTION Neuronal cell death and glial cell activation are the main pathological findings induced by seizures secondary to oxidative stress. Previous studies have explained neuronal cell death on the basis of cell necrosis and apoptosis. Recent studies have attributed the neuronal loss to autophagy. The proved antioxidant and antifibrotic effect of nilotinib favours its use in the management of epileptic seizures. AIM OF THE STUDY was to analyse the neuroprotective and antiepileptic effect of nilotinib and explain its mechanism of action. MATERIAL AND METHODS Forty adult male rats were divided into four groups: control, pentylenetetrazol (PTZ) group (injected with PTZ 60 mg/kg, s.c.), pregabalin (Pregb)-PTZ group (pretreated with pregabalin daily 30 mg/kg; orally for 1 week) and nilotinib (NIL)-PTZ group (pretreated with nilotinib, 25 mg/kg daily for 1 week) prior to PTZ. Seizure latency was evaluated, the hippocampus tissue level of antioxidant enzymes was assessed. The histopathological changes in the hippocampus were studied using hematoxylin and eosin stain and immunohistochemical stain for brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), beclin-1, nuclear factor kappa-B (NF-κB) and Bcl-2-like protein 4 (BAX). RESULTS Nilotinib induced an increase in the latency of seizures, enhanced the antioxidant levels of the γ-aminobutyric acid and nuclear factor (erythroid-derived 2)-like 2 activities together with the improvement of the hippocampal histology. A reduction was reported for BDNF, GFAP, beclin-1, NF-κB and BAX expression in nerve cells. CONCLUSIONS Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy.

中文翻译：

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尼罗替尼对戊四唑诱导的成年大鼠海马癫痫的神经保护作用：涉及氧化应激、自噬、炎症和细胞凋亡。

引言 神经元细胞死亡和神经胶质细胞活化是继发于氧化应激的癫痫发作引起的主要病理表现。以前的研究已经在细胞坏死和凋亡的基础上解释了神经元细胞的死亡。最近的研究将神经元损失归因于自噬。尼罗替尼经证实的抗氧化和抗纤维化作用有利于其用于治疗癫痫发作。本研究的目的是分析尼罗替尼的神经保护和抗癫痫作用并解释其作用机制。材料与方法 40只成年雄性大鼠分为四组：对照组、戊四唑（PTZ）组（注射PTZ 60 mg/kg，皮下注射）、普瑞巴林（Pregb）-PTZ组（每天30 mg/kg普瑞巴林预处理；口服） 1周）和尼罗替尼（NIL）-PTZ组（用尼罗替尼预处理，PTZ 之前，每天 25 mg/kg，持续 1 周）。评估癫痫发作潜伏期，评估海马组织抗氧化酶水平。使用苏木精和伊红染色以及脑源性神经营养因子 (BDNF)、胶质纤维酸性蛋白 (GFAP)、beclin-1、核因子 kappa-B (NF-κB) 和 Bcl 的免疫组织化学染色研究海马的组织病理学变化-2 样蛋白 4 (BAX)。结果尼罗替尼诱导癫痫发作潜伏期增加，增强γ-氨基丁酸和核因子（红细胞衍生2）样2活性的抗氧化水平，同时改善海马组织学。据报道，神经细胞中 BDNF、GFAP、beclin-1、NF-κB 和 BAX 的表达减少。