Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, USA.
Toxicol Sci. 2010 Aug;116(2):562-76. doi: 10.1093/toxsci/kfq137. Epub 2010 May 10.
Engineered nanoscale ceria is used as a diesel fuel catalyst. Little is known about its mammalian central nervous system effects. The objective of this paper is to characterize the biodistribution of a 5-nm citrate-stabilized ceria dispersion from blood into brain and its pro- or antioxidant effects. An approximately 4% aqueous ceria dispersion was iv infused into rats (0, 100, and up to 250 mg/kg), which were terminated after 1 or 20 h. Ceria concentration, localization, and chemical speciation in the brain were assessed by inductively coupled plasma mass spectrometry, light and electron microscopy (EM), and electron energy loss spectroscopy (EELS). Pro- or antioxidative stress effects were assessed as protein carbonyls, 3-nitrotyrosine, and protein-bound 4-hydroxy-2-trans-nonenal in hippocampus, cortex, and cerebellum. Glutathione reductase, glutathione peroxidase, manganese superoxide dismutase, and catalase levels and activities were measured in hippocampus. Catalase levels and activities were also measured in cortex and cerebellum. Na fluorescein and horseradish peroxidase (HRP) were given iv as blood-brain barrier (BBB) integrity markers. Mortality was seen after administration of 175-250 mg ceria/kg. Twenty hours after infusion of 100 mg ceria/kg, brain HRP was marginally elevated. EM and EELS revealed mixed Ce(III) and Ce(IV) valence in the freshly synthesized ceria in vitro and in ceria agglomerates in the brain vascular compartment. Ceria was not seen in microvascular endothelial or brain cells. Ceria elevated catalase levels at 1 h and increased catalase activity at 20 h in hippocampus and decreased catalase activity at 1 h in cerebellum. Compared with a previously studied approximately 30-nm ceria, this ceria was more toxic, was not seen in the brain, and produced little oxidative stress effect to the hippocampus and cerebellum. The results are contrary to the hypothesis that a smaller engineered nanomaterial would more readily permeate the BBB.
纳米级氧化铈被用作柴油燃料催化剂。目前人们对其在哺乳动物中枢神经系统中的作用知之甚少。本文旨在描述一种 5nm 柠檬酸稳定的氧化铈分散体从血液进入大脑的生物分布情况及其潜在的抗氧化或促氧化作用。将约 4%的水合氧化铈分散体静脉内输注到大鼠（0、100 和高达 250mg/kg）中，1 或 20 小时后处死大鼠。通过电感耦合等离子体质谱、光镜和电子显微镜（EM）以及电子能量损失谱（EELS）评估脑内的铈浓度、定位和化学形态。通过海马、皮质和小脑的蛋白质羰基、3-硝基酪氨酸和蛋白质结合的 4-羟基-2-反式-壬烯醛评估促氧化或抗氧化应激作用。测量海马中的谷胱甘肽还原酶、谷胱甘肽过氧化物酶、锰超氧化物歧化酶和过氧化氢酶的水平和活性。还测量了皮质和小脑中的过氧化氢酶水平和活性。静脉内给予荧光素钠和辣根过氧化物酶（HRP）作为血脑屏障（BBB）完整性标志物。给予 175-250mg/kg 氧化铈后出现死亡率。输注 100mg/kg 氧化铈 20 小时后，脑 HRP 略有升高。EM 和 EELS 显示在体外新合成的氧化铈和脑血管隔室中的氧化铈聚集体中存在混合的 Ce(III)和 Ce(IV)价。在微血管内皮细胞或脑细胞中未观察到氧化铈。氧化铈在 1 小时时升高了过氧化氢酶的水平，在 20 小时时增加了过氧化氢酶的活性，在 1 小时时降低了小脑的过氧化氢酶活性。与之前研究的约 30nm 氧化铈相比，这种氧化铈毒性更大，在大脑中未被观察到，并且对海马和小脑的氧化应激作用较小。结果与小尺寸的工程纳米材料更容易穿透血脑屏障的假设相反。
