Abdel-Wahab Basel A, Shaikh Ibrahim A, Khateeb Masood M, Habeeb Shafiuddin M
Department of Pharmacology, College of Medicine, Assiut University, Assiut, Egypt; Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia.
Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia.
Pharmacol Biochem Behav. 2015 Aug;135:105-13. doi: 10.1016/j.pbb.2015.05.020. Epub 2015 Jun 1.
Levetiracetam (LEV) is a unique, effective, relatively safe antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). This study aimed to explore the effect of combined treatment of LEV with omega 3 (OM3) on cognitive impairment and hippocampal oxidative stress and DNA damage induced by seizures in the PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats pretreated with single and combined treatment of LEV (30mg/kg, i.p.) and OM3 (200mg/kg, p.o.). Pretreatment with LEV and OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, the increase in hippocampal glutamate, malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase and superoxide dismutase activities induced by PTZ kindling, significantly decreased. These effects were higher with combined treatment of LEV with OM3 and significantly more than the observed effects of single LEV or OM3. In conclusion, the combined treatment of LEV with OM3 is more effective in seizure control and alleviating the cognitive impairment induced by PTZ kindling in the young rat model, the effects that result from the decrease in hippocampal oxidative stress and DNA damage which can be attributed to the antioxidant properties of both LEV and OM3. These results may be promising for the use of LEV and OM3 combination in the treatment of epileptic children.
左乙拉西坦（LEV）是一种独特、有效且相对安全的抗癫痫药物，它优先与突触囊泡蛋白2A（SV2A）相互作用。本研究旨在探讨左乙拉西坦与ω-3（OM3）联合治疗对戊四氮点燃的幼鼠模型中癫痫发作所致认知障碍、海马氧化应激和DNA损伤的影响。对接受左乙拉西坦（30mg/kg，腹腔注射）和OM3（200mg/kg，口服）单一及联合治疗预处理的戊四氮点燃幼鼠进行认知功能、氧化应激生物标志物和DNA损伤评估。在戊四氮点燃的大鼠中，以测试剂量的左乙拉西坦和OM3预处理可显著减轻戊四氮诱导的癫痫发作，并在被动回避和高架十字迷宫试验中降低认知障碍。此外，戊四氮点燃诱导的海马谷氨酸、丙二醛和8-羟基-2-脱氧鸟苷（8-OHdG）水平升高，以及还原型谷胱甘肽（GSH）水平、GSH过氧化物酶和超氧化物歧化酶活性降低均显著减少。左乙拉西坦与OM3联合治疗的效果更显著，明显优于单独使用左乙拉西坦或OM3的观察效果。总之，在幼鼠模型中，左乙拉西坦与OM3联合治疗在控制癫痫发作和减轻戊四氮点燃所致认知障碍方面更有效，其效果源于海马氧化应激和DNA损伤的减少，这可归因于左乙拉西坦和OM3的抗氧化特性。这些结果可能为左乙拉西坦和OM3联合用于治疗癫痫儿童带来希望。
