Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials

Taisuke Tomonaga; Hiroto Izumi; Takako Oyabu; Byeong-Woo Lee; Masaru Kubo; Manabu Shimada; Shingo Noguchi; Chinatsu Nishida; Kazuhiro Yatera; Yasuo Morimoto

doi:10.3390/nano10081563

Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials

Nanomaterials (Basel). 2020 Aug 9;10(8):1563. doi: 10.3390/nano10081563.

Authors

Affiliations

¹ Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
² Department of Chemical Engineering, Graduate School of Engineering, Hiroshima University, 4-1 Kagamiyama 1-chome, Higashi-Hiroshima-shi, Hiroshima 739-8527, Japan.
³ Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

Abstract

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/m³) 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 SiO₂ 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.

Keywords: CINC; biomarker; cytokine-induced neutrophil chemoattractant; inhalation exposure; intratracheal instillation; nanomaterial; pulmonary toxicity; rat.

Grants and funding

Nothing/''Development of Innovative Methodology for Safety Assessment of Industrial Nanomaterials'' by the Ministry of Economy, Trade and Industry (METI) of Japan.