Łukawski Krzysztof, Czuczwar Stanisław J
Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland.
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland.
Antioxidants (Basel). 2023 May 5;12(5):1049. doi: 10.3390/antiox12051049.
Free radicals are generated in the brain, as well as in other organs, and their production is proportional to the brain activity. Due to its low antioxidant capacity, the brain is particularly sensitive to free radical damage, which may affect lipids, nucleic acids, and proteins. The available evidence clearly points to a role for oxidative stress in neuronal death and pathophysiology of epileptogenesis and epilepsy. The present review is devoted to the generation of free radicals in some animal models of seizures and epilepsy and the consequences of oxidative stress, such as DNA or mitochondrial damage leading to neurodegeneration. Additionally, antioxidant properties of antiepileptic (antiseizure) drugs and a possible use of antioxidant drugs or compounds in patients with epilepsy are reviewed. In numerous seizure models, the brain concentration of free radicals was significantly elevated. Some antiepileptic drugs may inhibit these effects; for example, valproate reduced the increase in brain malondialdehyde (a marker of lipid peroxidation) concentration induced by electroconvulsions. In the pentylenetetrazol model, valproate prevented the reduced glutathione concentration and an increase in brain lipid peroxidation products. The scarce clinical data indicate that some antioxidants (melatonin, selenium, vitamin E) may be recommended as adjuvants for patients with drug-resistant epilepsy.
自由基在大脑以及其他器官中产生，其产生量与大脑活动成正比。由于大脑的抗氧化能力较低，所以它对自由基损伤特别敏感，自由基损伤可能会影响脂质、核酸和蛋白质。现有证据清楚地表明氧化应激在神经元死亡以及癫痫发生和癫痫的病理生理学中起作用。本综述致力于探讨在一些癫痫和癫痫发作的动物模型中自由基的产生以及氧化应激的后果，如导致神经退行性变的DNA或线粒体损伤。此外，还综述了抗癫痫（抗惊厥）药物的抗氧化特性以及抗氧化药物或化合物在癫痫患者中的可能用途。在众多癫痫发作模型中，大脑中自由基的浓度显著升高。一些抗癫痫药物可能会抑制这些作用；例如，丙戊酸盐降低了电惊厥诱导的大脑丙二醛（脂质过氧化的标志物）浓度的升高。在戊四氮模型中，丙戊酸盐可防止谷胱甘肽浓度降低以及大脑脂质过氧化产物增加。稀少的临床数据表明，一些抗氧化剂（褪黑素、硒、维生素E）可作为耐药性癫痫患者的辅助治疗药物。
