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Int. J. Mol. Sci. 2015, 16(1), 660-676; doi:10.3390/ijms16010660

Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs

1
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
2
Department of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, Japan
3
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
4
Department of Electrical and Electronic Engineering, Okayama University, Okayama 700-8530, Japan
5
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan
6
Department of Immunology, Mie University School of Medicine, Tsu 514-8507, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Bing Yan
Received: 16 September 2014 / Accepted: 16 December 2014 / Published: 30 December 2014
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Abstract

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs. View Full-Text
Keywords: zinc oxide nanoparticles; metal fume fever; pulmonary fibrosis; bleomycin; animal model zinc oxide nanoparticles; metal fume fever; pulmonary fibrosis; bleomycin; animal model
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wu, W.; Ichihara, G.; Hashimoto, N.; Hasegawa, Y.; Hayashi, Y.; Tada-Oikawa, S.; Suzuki, Y.; Chang, J.; Kato, M.; D'Alessandro-Gabazza, C.N.; Gabazza, E.C.; Ichihara, S. Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs. Int. J. Mol. Sci. 2015, 16, 660-676.

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