Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations
Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations
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DOI：
10.1080/1028415x.2016.1183342
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
Sharma, Deepak
中科院分区：
文献类型：
--
作者：
Das, Jharana;Singh, Rameshwar;Sharma, Deepak
背景：创伤性癫痫的定义是继发于严重脑损伤的反复发作。虽然药物被发现可以有效地控制癫痫发作，但长期使用它们会增加动物体内的活性氧。黄非瑟酮，一种天然生物活性植物营养素，在实验性癫痫模型中具有抗惊厥作用。目的：研究非瑟酮对铁致创伤性癫痫大鼠痫样电活动的影响及其可能的机制。方法：非瑟酮预处理（20 mg/kg体重，p.o.）选择大鼠12周，然后立体定向注射铁（5 μ l，100 mM）以产生铁诱导的癫痫。实验设计包括电生理研究（脑电图与皮层和海马CA 1区的多单位活动（MUA）相关;癫痫发作的频谱分析和癫痫相关行为研究（Morris水迷宫用于空间学习，旷场测试用于焦虑）和生化研究（脂质过氧化、Na+，K+-ATP酶活性）。非瑟酮预处理可阻止铁诱导的电惊厥的发展，并降低皮层相应的MUA（*P < 0.05）以及在海马中（*P < 0.001）。非瑟酮预处理可显著降低铁致痫大鼠的脂质过氧化物水平（P <0.05），保护Na+，K+-ATP酶活性（P < 0.05），减轻铁致痫大鼠的认知功能障碍。
Background: Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies.Objective: To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats.Methods: Fisetin pretreatment (20mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 mu l, 100mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na+,K+-ATPase activity) in both the cortex and the hippocampus.Results: Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P < 0.05) as well as in the hippocampus (***P < 0.001). Fisetin pretreatment decreased the lipid peroxides (*P < 0.05) and retained the Na+,K+-ATPase activity (*P < 0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions.Conclusion: This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.