Areecheewakul Sudartip, Adamcakova-Dodd Andrea, Givens Brittany E, Steines Benjamin R, Wang Yifang, Meyerholz David K, Parizek Nathanial J, Altmaier Ralph, Haque Ezazul, O'Shaughnessy Patrick T, Salem Aliasger K, Thorne Peter S
Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, IA 52246, USA.
Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52246, USA.
NanoImpact. 2020 Apr;18. doi: 10.1016/j.impact.2020.100214. Epub 2020 Feb 20.
Characterizations and toxicity screening were performed on metal oxide engineered nanomaterials (ENMs) independently comprising ZnO, CuO, CeO, FeO, WO, VO, TiO, AlO and MgO. Nanomaterials that exhibited the highest toxicity responses in the screening assays (ZnO, CuO, and VO) and the lesser explored material WO were tested for acute pulmonary toxicity . Female and male mice (C57Bl/6J) were exposed to aerosolized metal oxide ENMs in a nose-only exposure system and toxicity outcomes (biomarkers of cytotoxicity, immunotoxicity, inflammation, and lung histopathology) at 4 and 24 h after the start of exposure were assessed. The studies were performed as part of the NIEHS Nanomaterials Health Implications Research consortium with the purpose of investigating the effects of ENMs on various biological systems. ENMs were supplied by the Engineered Nanomaterials Resource and Coordination Core. Among the ENMs studied, the highest toxicity was observed for CuO and ZnO NPs in both and acute models. Compared to sham-exposed controls, there was a significant increase in bronchoalveolar lavage neutrophils and proinflammatory cytokines and a loss of macrophage viability at both 4 h and 24 h for ZnO and CuO but not seen for VO or WO. These effects were observed in both female and male mice. The cell viability performed after exposure to ENMs and assessment of lung inflammation after acute inhalation exposure were shown to be sensitive endpoints to predict ENM acute toxicity.
对分别包含氧化锌（ZnO）、氧化铜（CuO）、氧化铈（CeO）、氧化亚铁（FeO）、氧化钨（WO）、氧化钒（VO）、二氧化钛（TiO）、氧化铝（AlO）和氧化镁（MgO）的金属氧化物工程纳米材料（ENMs）进行了表征和毒性筛选。对在筛选试验中表现出最高毒性反应的纳米材料（ZnO、CuO和VO）以及研究较少的材料WO进行了急性肺毒性测试。将雌性和雄性小鼠（C57Bl/6J）置于仅经鼻暴露系统中暴露于雾化的金属氧化物ENMs，并在暴露开始后4小时和24小时评估毒性结果（细胞毒性、免疫毒性、炎症的生物标志物以及肺组织病理学）。这些研究是作为美国国立环境卫生科学研究所纳米材料对健康影响研究联盟的一部分进行的，目的是调查ENMs对各种生物系统的影响。ENMs由工程纳米材料资源与协调核心提供。在所研究的ENMs中，在短期和急性模型中均观察到CuO和ZnO纳米颗粒的毒性最高。与假暴露对照组相比，ZnO和CuO在4小时和24小时时支气管肺泡灌洗中性粒细胞和促炎细胞因子均显著增加，巨噬细胞活力丧失，但VO或WO未见此现象。在雌性和雄性小鼠中均观察到了这些效应。暴露于ENMs后进行的细胞活力检测以及急性吸入暴露后肺炎症评估被证明是预测ENM急性毒性的敏感终点。
