过氧化物酶体增殖物激活受体α激动剂苯扎贝特在戊四氮诱导的点燃癫痫模型中的抗点燃作用
Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model.
作者信息
Saha Lekha, Bhandari Swati, Bhatia Alka, Banerjee Dibyajyoti, Chakrabarti Amitava
机构信息
Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh;
Department of Experimental Medicine and Biotechnology, Postgraduate Institute Of Medical Education & Research, Sector 12, Chandigarh, India.
出版信息
J Epilepsy Res. 2014 Dec 31;4(2):45-54. doi: 10.14581/jer.14011. eCollection 2014 Dec.
BACKGROUND AND PURPOSE
Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats.
METHODS
In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study.
RESULTS
In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats.
CONCLUSIONS
These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy.
背景与目的
动物研究表明，过氧化物酶体增殖物激活受体（PPARs）可能参与癫痫控制，PPARα或PPARγ的选择性激动剂可提高癫痫阈值。本研究旨在评估苯扎贝特（一种过氧化物酶体增殖物激活受体α（PPAR-α）激动剂）在戊四氮（PTZ）诱导的大鼠癫痫点燃模型中的抗点燃作用及其机制。
方法
在PTZ点燃的Wistar大鼠模型中，在注射PTZ前30分钟腹腔注射不同剂量的苯扎贝特（100mg/kg、200mg/kg和300mg/kg）。每隔一天注射PTZ，直到动物完全点燃或直至10周。测量的参数包括点燃的潜伏期和点燃发生率、海马组织病理学研究、海马脂质过氧化研究、血清神经元特异性烯醇化酶以及海马DNA片段化研究。
结果
在本研究中，苯扎贝特显著降低了PTZ处理大鼠的点燃发生率，并显著延长了癫痫发作的潜伏期。在本研究中，苯扎贝特降低了硫代巴比妥酸反应性物质即丙二醛水平，增加了脑中还原型谷胱甘肽水平、过氧化氢酶和超氧化物歧化酶活性。这增加了其额外的神经保护作用。苯扎贝特还减少了脑中海马区的神经元损伤和细胞凋亡。因此，苯扎贝特在PTZ诱导的大鼠点燃模型中发挥了抗惊厥特性。
结论
这些发现可能有助于深入了解苯扎贝特作为抗点燃剂的机制，并可为预防PTZ诱导的癫痫发作的基础抗癫痫治疗提供有用的支持，表明其在颞叶癫痫治疗中的潜在应用价值。
Zotero 插件