Sisler Jennifer D, Pirela Sandra V, Shaffer Justine, Mihalchik Amy L, Chisholm William P, Andrew Michael E, Schwegler-Berry Diane, Castranova Vincent, Demokritou Philip, Qian Yong
*Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
Department of Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia 26505.
Toxicol Sci. 2016 Apr;150(2):418-28. doi: 10.1093/toxsci/kfw005. Epub 2016 Jan 14.
Cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles are 2 metal oxide nanoparticles with different redox potentials according to their semiconductor properties. By utilizing these two nanoparticles, this study sought to determine how metal oxide nanoparticle's mode of toxicological action is related to their physio-chemical properties in human small airway epithelial cells (SAEC). We investigated cellular toxicity, production of superoxide radicals and alterations in gene expression related to oxidative stress, and cellular death at 6 and 24 h following exposure to CoO and La2O3(administered doses: 0, 5, 25, and 50 µg/ml) nanoparticles. CoO nanoparticles induced gene expression related to oxidative stress at 6 h. After characterizing the nanoparticles, transmission electron microscope analysis showed SAEC engulfed CoO and La2O3nanoparticles. CoO nanoparticles were toxic after 6 and 24 h of exposure to 25.0 and 50.0 µg/ml administered doses, whereas, La2O3nanoparticles were toxic only after 24 h using the same administered doses. Based upon the Volumetric Centrifugation Methodin vivoSedimentation, Diffusion, and Dosimetry, the dose of CoO and La2O3nanoparticles delivered at 6 and 24 h were determined to be: CoO: 1.25, 6.25, and 12.5 µg/ml; La2O3: 5, 25, and 50 µg/ml and CoO: 4, 20, and 40 µg/ml; and La2O3: 5, 25, 50 µg/ml, respectively. CoO nanoparticles produced more superoxide radicals and caused greater stimulation of total tyrosine and threonine phosphorylation at both 6 and 24 h when compared with La2O3nanoparticles. Taken together, these data provide evidence that different toxicological modes of action were involved in CoO and La2O3metal oxide nanoparticle-induced cellular toxicity.
根据其半导体特性,一氧化碳钴(CoO)和氧化镧(La2O3)纳米颗粒是两种具有不同氧化还原电位的金属氧化物纳米颗粒。通过利用这两种纳米颗粒,本研究旨在确定金属氧化物纳米颗粒的毒理学作用模式如何与其在人小气道上皮细胞(SAEC)中的物理化学性质相关。我们研究了细胞毒性、超氧自由基的产生以及与氧化应激相关的基因表达变化,以及在暴露于CoO和La2O3(给药剂量:0、5、25和50μg/ml)纳米颗粒后6小时和24小时的细胞死亡情况。CoO纳米颗粒在6小时时诱导了与氧化应激相关的基因表达。在对纳米颗粒进行表征后,透射电子显微镜分析显示SAEC吞噬了CoO和La2O3纳米颗粒。CoO纳米颗粒在暴露于25.0和50.0μg/ml给药剂量6小时和24小时后具有毒性,而La2O3纳米颗粒仅在使用相同给药剂量24小时后具有毒性。根据体内体积离心法沉降、扩散和剂量测定,在6小时和24小时时递送的CoO和La2O3纳米颗粒剂量分别确定为:CoO:1.25、6.25和12.5μg/ml;La2O3:5、25和50μg/ml以及CoO:4、20和40μg/ml;La2O3:5、25、50μg/ml。与La2O3纳米颗粒相比,CoO纳米颗粒在6小时和24小时时产生了更多的超氧自由基,并引起了总酪氨酸和苏氨酸磷酸化的更大刺激。综上所述,这些数据提供了证据,表明CoO和La2O3金属氧化物纳米颗粒诱导的细胞毒性涉及不同的毒理学作用模式。