Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky Academic Medical Center, University of Kentucky, Lexington, Kentucky 40536-0596, USA.
Toxicol Sci. 2012 May;127(1):256-68. doi: 10.1093/toxsci/kfs067. Epub 2012 Feb 23.
Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes.
纳米氧化铈被用作柴油燃料的催化剂、印刷电路板制造中的研磨剂，并被作为抗氧化治疗剂进行研究。我们的目的是扩展先前的研究结果，即在单次给予纳米氧化铈后 30 天内，单核吞噬细胞（网状内皮系统）器官中的铈没有减少。一种约 5%的柠檬酸稳定的 30nm 氧化铈的水性分散体，在体内合成和表征，或载体，被静脉输注到大鼠中，在 1、7、30 或 90 天后终止。每天在笼边观察，每周测量体重。在两周内定量测量每日尿和粪便中的铈排泄量。称重 9 个器官，并从 14 个组织/器官/系统、血液和脑脊液中收集样本，以测定铈。评估组织学和氧化应激。在最初的两周内，不到 1%的纳米氧化铈被排泄，98%通过粪便排泄。体重增加最初受到损害。在一些氧化铈处理组中，脾脏重量显著增加，伴有异常。氧化铈主要保留在脾脏、肝脏和骨髓中。在 90 天内，任何组织中的铈含量都没有明显减少。肝脏中观察到肉芽肿。在肝脏和脾脏中观察到与时间相关的氧化应激变化。单核吞噬细胞系统的器官中持续保留纳米氧化铈，伴有不良变化。结果支持对惰性纳米尺度金属氧化物的长期命运和不良反应的担忧，这些氧化物分布在全身，持续保留，并产生不良反应。
