Morimoto Yasuo, Izumi Hiroto, Yoshiura Yukiko, Tomonaga Taisuke, Lee Byeong-Woo, Okada Takami, Oyabu Takako, Myojo Toshihiko, Kawai Kazuaki, Yatera Kazuhiro, Shimada Manabu, Kubo Masaru, Yamamoto Kazuhiro, Kitajima Shinichi, Kuroda Etsushi, Horie Masanori, Kawaguchi Kenji, Sasaki Takeshi
a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
b Hiroshima University , Higashi-Hiroshima , Japan .
Nanotoxicology. 2016;10(5):607-18. doi: 10.3109/17435390.2015.1104740. Epub 2015 Nov 11.
In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of NiO or TiO2. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the single intratracheal instillation. In the inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65, 1.84 mg/m(3), respectively) for 4 weeks. The same endpoints were examined from 3 days to 3 months after the end of exposure. Inhalation of NiO induced an increase in the number of neutrophils in BALF and concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and heme oxygenase (HO)-1. Intratracheal instillation of NiO induced persistent inflammation and upregulation of these cytokines was observed in the rats. However, inhalation of TiO2 did not induce pulmonary inflammation, and intratracheal instillation of TiO2 transiently induced an increase in the number of neutrophils in BALF and the concentrations of CINC-1, CINC-2 and HO-1. Taken together, a difference in pulmonary inflammation was observed between the high and low toxicity nanomaterials in the intratracheal instillation studies, as in the inhalation studies, suggesting that intratracheal instillation studies may be useful for ranking the harmful effects of nanoparticles.
为了研究气管内滴注研究是否有助于确定纳米颗粒的有害影响，我们使用相同纳米颗粒的样本进行了吸入和气管内滴注研究。分别使用氧化镍纳米颗粒（NiO）和二氧化钛纳米颗粒（TiO2）作为高毒性和低毒性的化学物质。在气管内滴注研究中，将大鼠暴露于0.2或1毫克的NiO或TiO2。在单次气管内滴注后的3天至6个月内，对支气管肺泡灌洗液（BALF）中的细胞分析和趋化因子进行了分析。在吸入研究中，将大鼠暴露于吸入的NiO或TiO2（分别为1.65、1.84毫克/立方米）中4周。在暴露结束后的3天至3个月内检查相同的终点指标。吸入NiO导致BALF中中性粒细胞数量增加以及细胞因子诱导的中性粒细胞趋化因子（CINC）-1、CINC-2和血红素加氧酶（HO）-1浓度升高。气管内滴注NiO可诱导大鼠持续炎症，并观察到这些细胞因子上调。然而，吸入TiO2未诱导肺部炎症，气管内滴注TiO2可短暂诱导BALF中中性粒细胞数量增加以及CINC-1、CINC-2和HO-1浓度升高。综上所述，与吸入研究一样，在气管内滴注研究中观察到高毒性和低毒性纳米材料之间肺部炎症存在差异，这表明气管内滴注研究可能有助于对纳米颗粒的有害影响进行排名。
