Kumar Puneet, Padi Satyanaryana Sreenivasulu Venketswera, Naidu Pattipati Sreenivasulu, Kumar Anil
Pharmacology Division, University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh, India.
Behav Pharmacol. 2006 Sep;17(5-6):485-92. doi: 10.1097/00008877-200609000-00014.
Huntington's disease is a progressive, degenerative disease characterized by abnormal body movements called chorea, and a reduction of various mental abilities. 3-Nitropropionic acid, an inhibitor of complex II of the electron transport chain, causes Huntington's disease-like symptoms in rodents. Recently, it has been reported that oxidative stress, which is one of the pathological hallmarks of various neurodegenerative disorders, also plays an important role in the pathogenesis of Huntington's disease. The present study was designed to investigate effects of resveratrol, an antioxidant with cyclooxygenase I inhibitory activity, in the 3-nitropropionic acid-induced model of Huntington's disease. Intraperitoneal administration of 3-nitropropionic acid (20 mg/kg for 4 days) caused significant loss of body weight, a decline in motor function (locomotor activity, movement pattern and vacuous chewing movements) and poor retention of memory. Repeated treatment with resveratrol (5 and 10 mg/kg, orally), once daily for a period of 8 days beginning 4 days prior to 3-nitropropionic acid administration, significantly improved the 3-nitropropionic acid-induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-nitropropionic acid administration significantly increased lipid peroxidation, nitrite levels, and depleted reduced glutathione levels, and decreased succinate dehydrogenase activity in the brains of rats. The results of the present study indicate that resveratrol (5 and 10 mg/kg, orally) significantly reversed 3-nitropropionic acid-induced motor and cognitive impairment, and that the beneficial effects of resveratrol might be attributed to its antioxidant activity.
亨廷顿舞蹈症是一种进行性退行性疾病，其特征为出现称为舞蹈病的异常身体运动以及各种心智能力减退。3-硝基丙酸是电子传递链复合物II的抑制剂，可在啮齿动物中引发类似亨廷顿舞蹈症的症状。最近，有报道称氧化应激作为各种神经退行性疾病的病理标志之一，在亨廷顿舞蹈症的发病机制中也起重要作用。本研究旨在调查白藜芦醇（一种具有环氧合酶I抑制活性的抗氧化剂）在3-硝基丙酸诱导的亨廷顿舞蹈症模型中的作用。腹腔注射3-硝基丙酸（20毫克/千克，共4天）导致体重显著减轻、运动功能下降（运动活性、运动模式和空嚼运动）以及记忆保持不佳。在3-硝基丙酸给药前4天开始，每天一次对白藜芦醇（5和10毫克/千克,口服）进行为期8天的重复治疗，可显著改善3-硝基丙酸诱导的运动和认知障碍。生化分析显示，全身性给予3-硝基丙酸可显著增加脂质过氧化、亚硝酸盐水平，并耗尽大鼠大脑中还原型谷胱甘肽水平，同时降低琥珀酸脱氢酶活性。本研究结果表明，白藜芦醇（5和10毫克/千克,口服）可显著逆转3-硝基丙酸诱导的运动和认知障碍，白藜芦醇的有益作用可能归因于其抗氧化活性。
