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三叶木通调节大脑海马区氧化毒性,对抗匹罗卡品诱导的小鼠癫痫持续状态。

Trichosanthes tricuspidata modulates oxidative toxicity in brain hippocampus against pilocarpine induced status epilepticus in mice.

机构信息

Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli, 620 024, Tamilnadu, India.

出版信息

Neurochem Res. 2013 Aug;38(8):1715-25. doi: 10.1007/s11064-013-1075-3. Epub 2013 May 18.

Abstract

Epilepsy prevails to be a neurological disorder in anticipation of safer drugs with enhanced anticonvulsant efficacy as presently available drugs fails to offer adequate control of epileptic seizures in about one-third of patients. The objective of this study was to evaluate the effect of Trichosanthes tricuspidata methanolic extract (TTME) against epilepsy mediated oxidative stress in pilocarpine induced mice. Intraperitonial administration of pilocarpine (85 mg/kg) induced seizure in mice was assessed by behavior observations, which is significantly (p < 0.05) reduced by TTME (100 and 200 mg/kg; i.p) in a dose dependant manner, similar to diazepam. Seizure was accompanied by significant increase in lipid peroxidation and the hippocampal nitrite content in pilocarpine group when compared with control. Moreover, the antioxidant enzymes superoxide dismutase, catalase and glutathione levels were decreased in pilocarpine administered groups. TTME administration attenuated oxidative damage as evident by decreased lipid oxidative damage and nitrite-nitrate content and restored the level of enzymatic antioxidant defenses in hippocampus. Involvement of free radicals during epilepsy is further confirmed by histopathological analysis which showed the loss of neuronal cells in hippocampus CA1 and CA3 pyramidal region. Our findings strongly support the hypothesis that TTME has anticonvulsant activity accompanied with the strong antioxidant potential plays a crucial role in reducing the oxidative stress produced by seizure.

摘要

癫痫被认为是一种神经系统疾病,需要寻找更安全、抗惊厥效果更好的药物,因为目前的药物无法充分控制大约三分之一患者的癫痫发作。本研究的目的是评估三叶鬼针草甲醇提取物 (TTME) 对匹鲁卡品诱导的小鼠癫痫介导的氧化应激的影响。通过行为观察评估腹腔内给予匹鲁卡品 (85mg/kg) 诱导的小鼠癫痫发作,TTME (100 和 200mg/kg;腹腔内) 以剂量依赖的方式显著降低 (p<0.05) 癫痫发作,与地西泮相似。与对照组相比,匹鲁卡品组的脂质过氧化和海马亚硝酸盐含量显著增加,伴随着癫痫发作。此外,给予匹鲁卡品后,抗氧化酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽水平降低。TTME 给药通过降低脂质氧化损伤和亚硝酸盐-硝酸盐含量减轻氧化损伤,并恢复海马中的酶抗氧化防御水平。组织病理学分析进一步证实了自由基在癫痫中的作用,该分析显示海马 CA1 和 CA3 锥体区神经元细胞丢失。我们的研究结果强烈支持以下假设:TTME 具有抗惊厥活性,同时具有强大的抗氧化潜力,在减少癫痫发作产生的氧化应激方面发挥着关键作用。

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