Experimental excitotoxicity provokes oxidative damage in mice brain and attenuation by extract of Asparagus racemosus
Experimental excitotoxicity provokes oxidative damage in mice brain and attenuation by extract of Asparagus racemosus
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DOI：
10.1007/s00702-003-0069-8
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发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
Hemnani, T
中科院分区：
文献类型：
--
作者：
Parihar, MS;Hemnani, T
兴奋毒性和氧化应激是阿尔茨海默病和帕金森病中发生的神经退行性疾病中神经元细胞死亡的主要机制。细胞外和细胞内通过多种机制产生的活性氧（reactive oxygen species，ROS）是引发和促进神经元退行性变的主要危险因素之一，因此寻找延缓或逆转神经元损伤的化合物具有重要意义。本研究旨在探讨总状芦笋提取物（AR）对海人酸（KA）诱导的海马和纹状体神经元损伤的保护作用。给予实验动物的AR提取物的剂量基于其总抗氧化活性的评价。AR提取物对Fe ~（3+）有较强的还原作用。通过海马内和纹状体内注射红藻氨酸（KA; 0.25 μ g，体积为0.5穆尔）至氯胺酮和甲苯噻嗪（200和2 mg/kg b.w.）分别）麻醉的小鼠。结果表明，KA注射后海马和纹状体区的脑损伤，标志着脂质过氧化和蛋白质羰基含量增加，谷胱甘肽过氧化物酶（GPx）活性和还原型谷胱甘肽（GSH）含量下降。补充AR提取物的小鼠表现出GPx活性和GSH含量的改善以及膜脂质过氧化和蛋白质羰基的减少。我们表明，AR提取物对氧化损伤的最小化作用，除了GPx活性和GSH含量的升高，最终可能导致对KA诱导的兴奋性毒性的保护作用。
Excitotoxicity and oxidative stress are the major mechanisms of neuronal cell death in neurodegenerative disorders that occurs in both Alzheimer's and Parkinson's diseases. Reactive oxygen species (ROS) that are generated extracellularly and intracellularly by various mechanisms are among the major risk factors that initiate and promote neurodegeneration.Therefore, it is important to find the compound which retard or reverse the neuronal injury. We designed this study to investigate the potential of extract of Asparagus racemosus (AR) against kainic acid (KA) - induced hippocampal and striatal neuronal damage. The dose of AR extract given to experimental animals was based on the evaluation of its total antioxidant activity. Extract of AR displayed potent reductant of Fe3+. The excitotoxic lesion in brain was produced by intra-hippocampal and intra-striatal injections of kainic acid (KA; 0.25 mug in a volume of 0.5 mul) to ketamine and xylazine (200 and 2 mg/kg b.w. respectively) anesthetized mice. The results showed impairment of hippocampus and striatal regions of brain after KA injection marked by an increase in lipid peroxidation and protein carbonyl content and decline in glutathione peroxidase (GPx) activity and reduced glutathione (GSH) content. The AR extract supplemented mice displayed an improvement in GPx activity and GSH content and reduction in membranal lipid peroxidation and protein carbonyl. We show that the minimizing effect of AR extract on oxidative damage in addition to the elevation of GPx activity and GSH content could eventually result in protective effect on the KA-induced excitotoxicity.