Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

doi:10.3390/ijms17081241

Open AccessArticle

Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation

by

Yasuo Morimoto

^1,*

,

Hiroto Izumi

¹,

Yukiko Yoshiura

¹,

Taisuke Tomonaga

¹,

Takako Oyabu

²,

Toshihiko Myojo

²,

Kazuaki Kawai

³,

Kazuhiro Yatera

⁴,

Manabu Shimada

⁵,

Masaru Kubo

⁵,

Kazuhiro Yamamoto

⁶,

Shinichi Kitajima

⁷,

Etsushi Kuroda

⁸

,

Kenji Kawaguchi

⁶ and

Takeshi Sasaki

⁶

¹

Department of Occupational Pneumology, 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 Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan

³

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan

⁴

Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan

⁵

Department of Chemical Engineering, Hiroshima University, Higashi-Hiroshima 739-8528, Japan

⁶

National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan

⁷

National Sanatorium Hoshizuka Keiaien, 4204 Hoshizuka-cho, Kanoya, Kagoshima 893-8502, Japan

⁸

Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, 6F IFReC Research Building, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2016, 17(8), 1241; https://doi.org/10.3390/ijms17081241

Submission received: 14 June 2016 / Revised: 7 July 2016 / Accepted: 22 July 2016 / Published: 1 August 2016

(This article belongs to the Special Issue Inorganic Nanostructures in Biological Systems)

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Abstract

We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m³) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

Keywords: zinc oxide; nanoparticle; CINC; neutrophil; intratracheal instillation; lung; inhalation

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MDPI and ACS Style

Morimoto, Y.; Izumi, H.; Yoshiura, Y.; Tomonaga, T.; Oyabu, T.; Myojo, T.; Kawai, K.; Yatera, K.; Shimada, M.; Kubo, M.; et al. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation. Int. J. Mol. Sci. 2016, 17, 1241. https://doi.org/10.3390/ijms17081241

AMA Style

Morimoto Y, Izumi H, Yoshiura Y, Tomonaga T, Oyabu T, Myojo T, Kawai K, Yatera K, Shimada M, Kubo M, et al. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation. International Journal of Molecular Sciences. 2016; 17(8):1241. https://doi.org/10.3390/ijms17081241

Chicago/Turabian Style

Morimoto, Yasuo, Hiroto Izumi, Yukiko Yoshiura, Taisuke Tomonaga, Takako Oyabu, Toshihiko Myojo, Kazuaki Kawai, Kazuhiro Yatera, Manabu Shimada, Masaru Kubo, and et al. 2016. "Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation" International Journal of Molecular Sciences 17, no. 8: 1241. https://doi.org/10.3390/ijms17081241

APA Style

Morimoto, Y., Izumi, H., Yoshiura, Y., Tomonaga, T., Oyabu, T., Myojo, T., Kawai, K., Yatera, K., Shimada, M., Kubo, M., Yamamoto, K., Kitajima, S., Kuroda, E., Kawaguchi, K., & Sasaki, T. (2016). Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation. International Journal of Molecular Sciences, 17(8), 1241. https://doi.org/10.3390/ijms17081241

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Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation

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