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N-乙酰半胱氨酸:对其影响苯妥英钠诱导惊厥作用的新认识。

N-acetyl cysteine: A new look at its effect on PTZ-induced convulsions.

机构信息

Faculty of Medicine, Department of Physiology, Izmir Katip Celebi University, Izmir, Turkey.

Faculty of Medicine, Department of Physiology, Izmir Katip Celebi University, Izmir, Turkey.

出版信息

Epilepsy Res. 2023 Jul;193:107144. doi: 10.1016/j.eplepsyres.2023.107144. Epub 2023 Apr 18.

DOI:10.1016/j.eplepsyres.2023.107144
PMID:37116249
Abstract

INTRODUCTION/AIM: Epilepsy is widely investigated as a common neurological disease requiring pharmacologically effective agents. N-acetyl cysteine (NAC), has become a remarkable molecule with its role in both antioxidant and glutaminergic modulation. There are many points and processes waiting to be revealed regarding the role of NAC in epilepsy.

MATERIALS AND METHODS

Pentylenetetrazole (PTZ) was administered to induce seizures in a total number of 48 Sprague-Dawley rats. 35 mg/kg PTZ dose as a sub-convulsive dose was administered to 24 animals to monitor EEG changes, while 70 mg/kg PTZ dose which was a convulsive dose was administered to 24 animals to determine seizure-related behavioral changes with the Racine's scale. 30 min before the seizure-induced procedure, NAC was administered at doses of 300 and 600 mg/kg as pretreatment to investigate anti-seizure and anti-oxidative effects. The spike percentage, the stage of convulsion, and the onset time of the first myoclonic jerk were evaluated to determine the anti-seizure effect. Furthermore, its effect on oxidative stress was determined by measuring both malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity.

RESULTS

There was a dose-dependent reduction in the seizure stage and prolonged onset time of the first myoclonic jerk in rats with NAC pretreatment. EEG recordings resulted in a dose-dependent decrease in spike percentages. Moreover, the same dose-dependent changes were observed in oxidative stress biomarkers, both 300 mg/kg NAC and 600 mg/kg decreased MDA levels and ameliorated SOD activity.

CONCLUSION

We can report that 300 mg/kg and 600 mg/kg doses of NAC are promising with their reducing effect on convulsions and have a beneficial effect by preventing oxidative stress. In addition, NAC has been also determined that this effect is dose-dependent. Detailed and comparative studies are needed on the convulsion-reducing effect of NAC in epilepsy.

摘要

简介/目的:癫痫作为一种常见的神经系统疾病,需要使用药理学有效的药物进行治疗,因此受到广泛研究。N-乙酰半胱氨酸(NAC)作为一种具有抗氧化和谷氨酰胺调节作用的重要分子,其作用机制有许多尚未被揭示的方面。

材料和方法

本研究共纳入 48 只 Sprague-Dawley 大鼠,腹腔注射戊四氮(PTZ)以诱导癫痫发作。24 只动物给予 35mg/kg 的 PTZ 剂量(亚惊厥剂量)以监测脑电图变化,24 只动物给予 70mg/kg 的 PTZ 剂量(惊厥剂量)以评估 Racine 量表相关的行为变化。在诱导癫痫发作前 30 分钟,给予 NAC 预处理,剂量分别为 300mg/kg 和 600mg/kg,以评估其抗癫痫和抗氧化作用。通过评估棘波百分比、惊厥分期和首次肌阵挛性抽搐的发作时间来评估抗癫痫作用,通过测量丙二醛(MDA)水平和超氧化物歧化酶(SOD)酶活性来评估其对氧化应激的影响。

结果

NAC 预处理可剂量依赖性地降低癫痫大鼠的惊厥分期并延长首次肌阵挛性抽搐的发作时间。脑电图记录显示棘波百分比呈剂量依赖性降低。此外,在氧化应激生物标志物方面也观察到了相同的剂量依赖性变化,NAC 的 300mg/kg 和 600mg/kg 剂量均降低 MDA 水平并改善 SOD 活性。

结论

我们可以报告,NAC 的 300mg/kg 和 600mg/kg 剂量具有降低癫痫发作的潜力,并通过预防氧化应激产生有益作用。此外,还确定了这种作用具有剂量依赖性。需要对 NAC 在癫痫中的抗惊厥作用进行详细和比较研究。

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