Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials
Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials
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DOI：
10.3390/nano10081563
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发表时间：
2020-08-01
期刊：
影响因子：
5.3
通讯作者：
Morimoto, Yasuo
中科院分区：
文献类型：
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作者：
Tomonaga, Taisuke;Izumi, Hiroto;Morimoto, Yasuo
本工作确定了细胞因子诱导的中性粒细胞趋化因子(CINC)-1、CINC-2和CINC-3是否可以作为预测纳米材料(NMS)高或低肺毒性的标志物。我们将二氧化镍(NiO)和二氧化铈(CeO2)的NMS分为高毒性，将二氧化钛(P90和金红石)和氧化锌(ZnO)的NMS归类为低毒，并分析了大鼠气管内滴入(0.2和1.0 mg)和吸入暴露(0.32-10.4 mg/m(3))材料(NiO、CeO2、TiO2(P90和金红石)、ZnO NMS和微米二氧化硅(SiO_2))后3天至6个月的支气管肺泡灌洗液(BALF)中CINCs的先前数据。NMS高、低肺毒性时BALF中CINC-1、CINC-2浓度有不同的升高趋势，并与BALF中其他炎症标志物呈正相关。然而，与CINC-1和CINC-2相比，CINC-3仅以剂量依赖的方式轻微增加。CINC-1和CINC-2对NMS毒性的受试者工作特性分析表明，CINC-1和CINC-2在暴露后1周或1个月时的毒性判别准确率最高，而气管内滴注SiO(2)后BALF中的CINC-1和CINC-2作为高毒性物质，可以准确地预测暴露后1个月以上的毒性。这些数据表明，CINC-1和CINC-2可能是预测NMS肺毒性的有用生物标志物，在气管内滴注和吸入暴露中都是相对较早的。
This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2(P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after intratracheal instillation (0.2 and 1.0 mg) and inhalation exposure (0.32-10.4 mg/m(3)) of materials (NiO, CeO2, TiO2(P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following intratracheal instillation of SiO(2)as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both intratracheal instillation and inhalation exposure.