Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi, India.
Basic Clin Pharmacol Toxicol. 2010 May;106(5):372-7. doi: 10.1111/j.1742-7843.2009.00499.x. Epub 2009 Dec 7.
The present study assessed the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemically induced epileptogenesis in rats. Epileptogenesis was induced by administration of pentylenetetrazole (30 mg/kg, s.c.) on alternate days (three times/week) for 9-11 weeks or until stage 4 of seizure score was achieved. The neurobehavioural parameters used for cognitive assessment were step-down latency in continuous avoidance apparatus and transfer latency in elevated plus maze test paradigm. Carbamazepine and lamotrigine were administered intraperitoneally in doses of 60 mg/kg and 25 mg/kg, respectively, according to the groups, once a day for 11 weeks. Oxidative stress was assessed in isolated homogenized whole brain samples and estimated for the levels of malondialdehyde, reduced glutathione, catalase and superoxide dismutase. The results showed that lamotrigine did not produce any change in cognitive function, while carbamazepine produced cognitive dysfunction. Cognitive decline seen in the carbamazepine-treated pentylenetetrazole-kindled group was also associated with increased oxidative stress. Lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group.
本研究评估了卡马西平和拉莫三嗪在戊四氮诱导的大鼠癫痫发生过程中对认知功能和大脑氧化应激的影响。癫痫发生通过隔日（每周三次）给予戊四氮（30mg/kg，sc）诱导 9-11 周或达到癫痫评分第 4 阶段。用于认知评估的神经行为参数是连续回避装置中的下台阶潜伏期和高架十字迷宫测试范式中的转移潜伏期。根据组别，卡马西平和拉莫三嗪分别以 60mg/kg 和 25mg/kg 的剂量腹膜内给药，每天一次，共 11 周。在分离的匀浆全脑样本中评估氧化应激，并估计丙二醛、还原型谷胱甘肽、过氧化氢酶和超氧化物歧化酶的水平。结果表明，拉莫三嗪对认知功能没有任何改变，而卡马西平则导致认知功能障碍。卡马西平治疗的戊四氮点燃组的认知下降也与氧化应激增加有关。拉莫三嗪单独治疗对氧化应激参数没有影响，但与戊四氮点燃的卡马西平治疗组相比，它显著降低了戊四氮点燃组的氧化应激。
