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锐钛矿相和金红石相二氧化钛纳米颗粒经鼻腔滴注后潜在的神经病变

Potential neurological lesion after nasal instillation of TiO(2) nanoparticles in the anatase and rutile crystal phases.

作者信息

Wang Jiangxue, Chen Chunying, Liu Ying, Jiao Fang, Li Wei, Lao Fang, Li Yufeng, Li Bai, Ge Cuicui, Zhou Guoqiang, Gao Yuxi, Zhao Yuliang, Chai Zhifang

机构信息

Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Lab of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, PR China.

出版信息

Toxicol Lett. 2008 Dec 15;183(1-3):72-80. doi: 10.1016/j.toxlet.2008.10.001. Epub 2008 Oct 17.

Abstract

Nanoscale titanium dioxide (TiO(2)) is massively produced and widely used in living environment, which hence make the potential risk to human health. Central nervous system (CNS) is the potential susceptible target of inhaled nanoparticles, but the studies on this aspect are limited so far. We report the accumulation and toxicity results in vivo of two crystalline phases of TiO(2) nanoparticles (80nm, rutile and 155nm, anatase; purity >99%). The female mice were intranasally instilled with 500microg of TiO(2) nanoparticles suspension every other day for 30 days. Synchrotron radiation X-ray fluorescence analysis (SRXRF) and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the contents of titanium in murine brain. Then, the pathological examination of brain tissue, oxidative stress-mediated responses, and levels of neurochemicals in the brain of exposed mice were also analyzed. The obvious morphological changes of hippocampal neurons and increased GFAP-positive astrocytes in the CA4 region were observed, which were in good agreements with higher Ti contents in the hippocampus region. Oxidative stress occurred obviously in whole brain of exposed mice such as lipid peroxidation, protein oxidation and increased activities of catalase, as well as the excessive release of glutamic acid and nitric oxide. These findings indicate anatase TiO(2) nanoparticles exhibited higher concern on some tested biological effects. To summarize, results provided the preliminary evidence that nasal instilled TiO(2) nanoparticles could be translocated into the central nervous system and cause potential lesion of brain, and the hippocampus would be the main target within brain.

摘要

纳米级二氧化钛(TiO₂)大量生产并广泛应用于生活环境中,因此对人类健康存在潜在风险。中枢神经系统(CNS)是吸入纳米颗粒的潜在易感靶点,但目前这方面的研究有限。我们报告了两种晶相的TiO₂纳米颗粒(80nm,金红石型和155nm,锐钛矿型;纯度>99%)在体内的积累和毒性结果。雌性小鼠每隔一天经鼻滴注500μg TiO₂纳米颗粒悬浮液,持续30天。使用同步辐射X射线荧光分析(SRXRF)和电感耦合等离子体质谱(ICP-MS)来测定小鼠脑中钛的含量。然后,还分析了暴露小鼠脑组织的病理检查、氧化应激介导的反应以及脑中神经化学物质的水平。观察到海马神经元明显的形态变化以及CA4区域GFAP阳性星形胶质细胞增加,这与海马区域较高的钛含量一致。暴露小鼠的全脑明显发生氧化应激,如脂质过氧化、蛋白质氧化和过氧化氢酶活性增加,以及谷氨酸和一氧化氮的过度释放。这些发现表明锐钛矿型TiO₂纳米颗粒在一些测试的生物学效应方面表现出更高的关注度。总之,结果提供了初步证据,即经鼻滴注的TiO₂纳米颗粒可转移至中枢神经系统并导致潜在的脑损伤,海马将是脑内的主要靶点。

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