Yadav Rajesh S, Sankhwar Madhu Lata, Shukla Rajendra K, Chandra Ramesh, Pant Aditya B, Islam Fakhrul, Khanna Vinay K
Indian Institute of Toxicology Research, (Council of Scientific and Industrial Research, New Delhi), Post Box 80, MG Marg, Lucknow-226001, India.
Toxicol Appl Pharmacol. 2009 Nov 1;240(3):367-76. doi: 10.1016/j.taap.2009.07.017. Epub 2009 Jul 23.
In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.
鉴于砷的持续暴露以及相关的人类健康风险，包括神经毒性，已在大鼠中研究了多酚类抗氧化剂姜黄素的神经保护功效。与对照组相比，用砷（亚砷酸钠，20毫克/千克体重，口服，28天）处理的大鼠的运动活性、握力（降低26%）和转棒试验表现（降低82%）显著下降。经砷处理的大鼠纹状体中多巴胺受体结合（降低32%）以及纹状体中酪氨酸羟化酶（TH）免疫反应性（降低19%）也有所下降。与对照组相比，经砷处理的大鼠纹状体（6.5倍）、额叶皮质（6.3倍）和海马体（7.0倍）中的砷水平升高，且这些脑区的氧化应激增强，表现为脂质过氧化、蛋白质羰基增加，谷胱甘肽水平、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性降低，且存在差异效应。与经砷处理的大鼠相比，同时用砷（亚砷酸钠，20毫克/千克体重，口服，28天）和姜黄素（100毫克/千克体重，口服，28天）处理导致运动活性和握力增加，转棒试验表现得到改善。与单独用砷处理的大鼠相比，联合处理的大鼠这些脑区的纹状体多巴胺受体结合和TH表达增加，而砷水平和氧化应激降低。与对照组相比，单独用姜黄素（100毫克/千克体重，口服，28天）处理的大鼠对这些参数均无显著影响。同时用砷和姜黄素处理的大鼠在行为、神经化学和免疫组织化学参数方面得到显著保护，表明姜黄素具有神经保护功效。
