Dhediya Rajnish M, Joshi Shirish S, Gajbhiye Snehalata V, Jalgaonkar Sharmila V, Biswas Mansij
Department of Pharmacology & Therapeutics, Seth GSMC & KEM Hospital, Parel, Mumbai, Maharashtra 400 012, India.
Department of Pharmacology & Therapeutics, Seth GSMC & KEM Hospital, Parel, Mumbai, Maharashtra 400 012, India.
Epilepsy Behav. 2016 Aug;61:153-157. doi: 10.1016/j.yebeh.2016.05.024. Epub 2016 Jun 23.
Epilepsy is the third most common cause of neurological disability worldwide. Despite the introduction of antiepileptic drugs (AEDs) in the past 20years, the seizures of around 30% of patients with epilepsy remain refractory to available treatment. Also, available AEDs and the disease itself have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. S-adenosyl methionine has potential antiepileptic and memory-enhancing properties because of its involvement in the transmethylation reaction.
The present study was designed to evaluate the antiepileptic effect of S-adenosyl methionine and its role in memory impairment in the pentylenetetrazole (PTZ)-induced kindling model in rats.
The antiepileptic effect of 2 doses of SAM (50 and 100mg/kg) was tested by evaluating seizure severity score and seizure latency in the pentylenetetrazole-induced kindling model in rats. At the end of the study, spatial memory was evaluated in an elevated plus maze (EPM) test, and animals were sacrificed for estimation of oxidative stress markers in brain tissue homogenate.
A higher dose of SAM (100mg/kg) exhibited an increase in seizure latency and a decrease in seizure severity score, suggesting its antiepileptic activity in the PTZ-induced kindling model. Also, the administration of SAM (50 and 100mg/kg) showed a decrease in transfer latency in the EPM test compared to the disease control group (p<0.0001). Biochemical analysis of rat brain tissue revealed significantly decreased malondialdehyde (p<0.0001) and increased glutathione (GSH) (p<0.0001) in the SAM 100-mg/kg group compared with that in the disease control group.
The results demonstrated that S-adenosyl methionine exerts antiepileptic, memory-enhancing, and antioxidant properties in a pentylenetetrazole-induced kindling model of epilepsy.
癫痫是全球第三大常见神经功能障碍病因。尽管在过去20年中引入了抗癫痫药物（AEDs），但约30%的癫痫患者的癫痫发作对现有治疗仍无反应。此外，现有的抗癫痫药物和疾病本身都有可能对认知功能产生有害影响，从而损害患者的健康。S-腺苷甲硫氨酸因其参与转甲基反应而具有潜在的抗癫痫和增强记忆的特性。
本研究旨在评估S-腺苷甲硫氨酸在戊四氮（PTZ）诱导的大鼠点燃模型中的抗癫痫作用及其在记忆损伤中的作用。
通过评估大鼠戊四氮诱导点燃模型中的癫痫严重程度评分和癫痫发作潜伏期，测试2种剂量的SAM（50和100mg/kg）的抗癫痫作用。在研究结束时，在高架十字迷宫（EPM）试验中评估空间记忆，并处死动物以估计脑组织匀浆中的氧化应激标志物。
较高剂量的SAM（100mg/kg）表现出癫痫发作潜伏期延长和癫痫严重程度评分降低，表明其在PTZ诱导的点燃模型中的抗癫痫活性。此外，与疾病对照组相比，SAM（50和100mg/kg）给药组在EPM试验中的转移潜伏期缩短（p<0.0001）。大鼠脑组织的生化分析显示，与疾病对照组相比，SAM 100mg/kg组的丙二醛显著降低（p<0.0001），谷胱甘肽（GSH）增加（p<0.0001）。
结果表明，S-腺苷甲硫氨酸在戊四氮诱导的癫痫点燃模型中具有抗癫痫、增强记忆和抗氧化特性。
