Department of Pharmacology and Drug Toxicology, Medical University-Plovdiv, 4002 Plovdiv, Bulgaria.
Department of Bioorganic Chemistry, Medical University-Plovdiv, 4002 Plovdiv, Bulgaria.
Int J Mol Sci. 2021 Feb 25;22(5):2264. doi: 10.3390/ijms22052264.
Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE.
Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus.
The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.
癫痫持续状态（SE）是一种以长时间癫痫活动为特征的神经系统疾病，随后会发生致痫过程。本研究旨在评估托吡酯（TPM）和拉科酰胺（LCM）治疗对匹鲁卡品诱导 SE 模型中氧化应激和炎症损伤的早期影响。
雄性 Wistar 大鼠随机分为六组，两种抗癫痫药物（AEDs），TPM（40 和 80 mg/kg，ip）和 LCM（10 和 30 mg/kg，ip），在匹鲁卡品给药后重复三次注射。SE 后 24 小时处死大鼠，研究海马氧化应激和炎症反应的多个参数。
与 SE-veh 组相比，两种药物 TPM 和 LCM，在使用的两种剂量下，在给药后 30 分钟均成功减轻了运动性癫痫发作的次数。与对照组相比，匹鲁卡品诱导的 SE 降低了超氧化物歧化酶（SOD）活性和还原型谷胱甘肽（GSH）水平，同时增加了过氧化氢酶（CAT）活性、丙二醛（MDA）和白细胞介素-1β（IL-1β）水平。SE 组不影响 TNF-α 水平。较高剂量 30mg/kg 的 LCM 将 SOD 活性恢复到 SE 组的对照水平。两种 AEDs 在应用的两种剂量下也使 CAT 活性和 MDA 水平正常化至对照值。总之，我们认为 TPM 和 LCM 的抗氧化作用可能有助于它们对抗匹鲁卡品诱导的 SE 的抗惊厥作用，而它们在海马中的弱抗炎作用是 SE 严重程度降低的结果。
