Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: A novel nitric oxide mechanism

Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: A novel nitric oxide mechanism
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DOI:
10.1016/j.fct.2009.07.011
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发表时间:
2009-10-01
影响因子:
4.3
通讯作者:
Kumar, Anil
Kumar, Anil
中科院分区:
农林科学2区
文献类型:
--
作者:
Kumar, Puneet;Kumar, Anil

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亨廷顿氏病是一种神经退行性疾病,其特征是舞蹈病和痴呆。目前还没有确切的治疗药物可以控制和治愈这种疾病。3-硝基丙酸是一种神经毒素,可引起动物的步态和记忆障碍,导致氧化损伤和谷胱甘肽防御功能紊乱,3-NP模型是开发适合治疗亨廷顿病的药物的有效工具。本研究比较了番茄红素和表没食子儿茶素-3-没食子酸酯(EGCG)对记忆障碍和谷胱甘肽系统对3-NP治疗的影响。在Morris水迷宫和升高+迷宫任务中,3-NP治疗显著损害了记忆。第15天,大鼠大脑纹状体、海马和皮质区还原型谷胱甘肽、总谷胱甘肽和谷胱甘肽- s转移酶水平均显著降低。番茄红素(2.5、5和10 mg/kg)和EGCG(10、20和40 mg/kg)处理显著改善了记忆,恢复了谷胱甘肽系统功能。此外,l -精氨酸和L-NAME预处理与亚有效剂量的番茄红素(5 mg/kg)和EGCG (20 mg/kg)分别逆转并增强了它们的保护作用。综上所述,番茄红素和EGCG可以通过参与一氧化氮途径来控制3-NP诱导的行为和生化改变。2009爱思唯尔有限公司版权所有。
Huntington's disease is a neurodegenerative disorder characterized by symptoms like chorea and dementia. There is no exact therapeutic agent available to manage and cure this disease. 3-Nitropropionic acid, a neurotoxin causes gait and memory impairment which leads to oxidative damage and upsets glutathione defense in animals, 3-NP model is a useful tool to develop suitable therapeutic agent in the treatment of Huntington's disease. Present study compares the effects of lycopene and epigallocatechin-3-gallate (EGCG) on memory impairment and disturbs glutathione system against 3-NP treatment. 3-NP treatment significantly impaired memory as assessed in Morris water maze and elevated plus maze tasks. On the 15 day, the levels of reduced glutathione, total glutathione and glutathione-S-transferase were also significantly decreased in the striatum, hippocampus and cortex areas of the brain. The treatment with lycopene (2.5, 5 and 10 mg/kg) and EGCG (10, 20 and 40 mg/kg) significantly improved memory and restored glutathione system functioning. Further, L-arginine and L-NAME pretreatment with the sub effective dose of lycopene (5 mg/kg) and EGCG (20 mg/kg) reversed and potentiate their protective effects respectively. In conclusion, lycopene and EGCG could be used to mange 3-NP induced behavioral and biochemical alterations by involving nitric oxide pathways. (C) 2009 Elsevier Ltd. All rights reserved.