Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: Possible role of nitric oxide

Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: Possible role of nitric oxide
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DOI:
10.1016/j.bbr.2009.08.028
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发表时间:
2010-01-05
影响因子:
2.7
通讯作者:
Kumar, Anil
Kumar, Anil
中科院分区:
心理学3区
文献类型:
--
作者:
Kumar, Puneet;Kumar, Anil

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3-硝基丙酸(3-NP)是研究亨廷顿病(HD)及其相关神经精神问题的著名实验模型。本研究旨在探讨橙皮苷、柚皮苷及其一氧化氮机制(如果有的话)对3-硝基丙酸诱导的大鼠神经毒性的保护作用。3-硝基丙酸(10 mg/kg)给药14天后,大鼠出现明显的HD样症状,表现为运动活动、体重、握力、氧化防御和纹状体线粒体复合酶(Complex-I、II和-IV)活性降低。3-NP处理组大鼠的行为改变、氧化应激反应和线粒体酶复合体功能障碍明显减轻,柚皮苷和橙皮苷预处理组的行为改变明显减轻。L精氨酸(50 mg/kg)预先给予小剂量橙皮苷(50 mg/kg)和柚皮苷(50 mg/kg)可明显减弱橙皮苷和柚皮苷的保护作用。而非选择性一氧化氮合酶抑制剂L-NAME(10 mg/kg)预先给予橙皮苷(50 mg/kg)和柚皮苷(50 mg/kg)可显著增强其保护作用,且与其本身的作用相比差异显著。研究强调了橙皮苷和柚皮苷对亨廷顿类似疾病的治疗潜力,并进一步表明这些药物可能通过一氧化氮机制发挥作用。(C)2009爱思唯尔B.V.保留所有权利。
3-Nitropropionic acid (3-NP) is a well known experimental model to study Huntington's disease (HD) and associated neuropsychiatric problems. Present study has been designed to explore the protective effects of hesperidin, naringin, and their nitric oxide mechanism (if any) against 3-nitropropionic acid induced neurotoxicity in rats.Systemic 3-nitropropionic acid (10 mg/kg) treatment for 14 days in rats significantly induced HD like symptoms in rats as indicated by reduced locomotor activity, body weight, grip strength, oxidative defense and mitochondrial complex enzymes (complex-I, II, and -IV) activities in striatum. Naringin and hesperidin pretreatment significantly attenuated behavioral alterations, oxidative stress and mitochondrial enzymes complex dysfunction in 3-NP treated group. L-Arginine (50 mg/kg) pretreatment with lower dose of hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly attenuated the protective effect of hesperidin and naringin respectively. Whereas L-NAME (10 mg/kg), a non-selective NOS inhibitor pretreatment with hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se. Study highlights the therapeutic potential of hesperidin and naringin against Huntington's like conditions and further indicates that these drugs might act through nitric oxide mechanism. (C) 2009 Elsevier B.V. All rights reserved.