Martinc Boštjan, Grabnar Iztok, Vovk Tomaž
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Curr Neuropharmacol. 2014 Dec;12(6):527-50. doi: 10.2174/1570159X12666140923205715.
Epilepsy is known as one of the most frequent neurological diseases, characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in pathways leading to neurodegeneration, which serves as the most important propagating factor, leading to the epileptic condition and cognitive decline. Moreover, there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy. A meta-analysis, conducted in the present review confirms an association between epilepsy and increased lipid peroxidation. Furthermore, it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation. Therefore, it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages, reduced epileptogenesis and milder cognitive deterioration. To evaluate this hypothesis studies investigating the neuroprotective therapeutic potential of various antioxidants in cells, animal seizure models and patients with epilepsy have been reviewed. Numerous beneficial effects of antioxidants on oxidative stress markers and in some cases also neuroprotective effects were observed in animal seizure models. However, despite these encouraging results, till now only a few antioxidants have been further applied to patients with epilepsy as an add-on therapy. Based on the several positive findings in animal models, a strong need for more carefully planned, randomized, double-blind, cross-over, placebo-controlled clinical trials for the evaluation of antioxidants efficacy in patients with epilepsy is warranted.
癫痫是最常见的神经系统疾病之一，其特征是具有产生癫痫发作的持久倾向。氧化应激被认为直接参与导致神经退行性变的途径，而神经退行性变是导致癫痫状态和认知衰退的最重要传播因素。此外，越来越多的证据表明癫痫患者抗氧化系统平衡受到干扰，进而导致活性物质生成增加。本综述中进行的一项荟萃分析证实了癫痫与脂质过氧化增加之间的关联。此外，还表明一些抗癫痫药物可能会额外增加脂质过氧化。因此，有理由提出在癫痫过程中，用抗氧化剂进行神经保护治疗可能会减少严重的结构损伤、减少癫痫发生并减轻认知恶化。为了评估这一假设，本文综述了研究各种抗氧化剂在细胞、动物癫痫模型和癫痫患者中的神经保护治疗潜力的研究。在动物癫痫模型中观察到抗氧化剂对氧化应激标志物有许多有益作用，在某些情况下还具有神经保护作用。然而，尽管有这些令人鼓舞的结果，但到目前为止，只有少数抗氧化剂作为辅助治疗进一步应用于癫痫患者。基于动物模型中的一些阳性发现，强烈需要进行更精心设计的随机、双盲、交叉、安慰剂对照临床试验，以评估抗氧化剂对癫痫患者的疗效。
