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Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs.

Wu W, Ichihara G, Hashimoto N, Hasegawa Y, Hayashi Y, Tada-Oikawa S, Suzuki Y, Chang J, Kato M, D'Alessandro-Gabazza CN, Gabazza EC, Ichihara S - Int J Mol Sci (2014)

Bottom Line: Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important.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 Article: PubMed Central - PubMed

Affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. wendyvvri@med.nagoya-u.ac.jp.

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.

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Representative optical micrographs of H&E-stained lung tissues. Mice were exposed to: (A) no ZnO; (B) 10 µg of ZnO; (C) 20 µg of ZnO nanoparticles without BLM treatment; (D) no ZnO; (E) 10 µg of ZnO and (F) 20 µg of ZnO nanoparticles with BLM treatment. Samples were collected at Day 14 after administration.
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ijms-16-00660-f005: Representative optical micrographs of H&E-stained lung tissues. Mice were exposed to: (A) no ZnO; (B) 10 µg of ZnO; (C) 20 µg of ZnO nanoparticles without BLM treatment; (D) no ZnO; (E) 10 µg of ZnO and (F) 20 µg of ZnO nanoparticles with BLM treatment. Samples were collected at Day 14 after administration.

Mentions: The recovery of pulmonary inflammation was observed at 14 days after administration. In the SALINE group, inflammatory infiltration in the alveolar septum recovered to normal lung architecture in mice exposed to 10 µg of ZnO nanoparticles, while a slight accumulation of inflammatory cells was noted in mice exposed to 20 µg of ZnO nanoparticles. In contrast, mild inflammation was evident in all mice of the BLM groups after exposure to ZnO nanoparticles (Figure 5 and Figure S1A). To check pulmonary fibrosis, Masson’s trichrome staining and alpha smooth muscle actin (α-SMA) immunohistochemistry were conducted using samples harvested on Day 14. It turns out that exposure to ZnO nanoparticles up to 20 µg had no obvious effects on collagen deposition or fibroblast proliferation, both in the SALINE and BLM groups (data not shown).


Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs.

Wu W, Ichihara G, Hashimoto N, Hasegawa Y, Hayashi Y, Tada-Oikawa S, Suzuki Y, Chang J, Kato M, D'Alessandro-Gabazza CN, Gabazza EC, Ichihara S - Int J Mol Sci (2014)

Representative optical micrographs of H&E-stained lung tissues. Mice were exposed to: (A) no ZnO; (B) 10 µg of ZnO; (C) 20 µg of ZnO nanoparticles without BLM treatment; (D) no ZnO; (E) 10 µg of ZnO and (F) 20 µg of ZnO nanoparticles with BLM treatment. Samples were collected at Day 14 after administration.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307267&req=5

ijms-16-00660-f005: Representative optical micrographs of H&E-stained lung tissues. Mice were exposed to: (A) no ZnO; (B) 10 µg of ZnO; (C) 20 µg of ZnO nanoparticles without BLM treatment; (D) no ZnO; (E) 10 µg of ZnO and (F) 20 µg of ZnO nanoparticles with BLM treatment. Samples were collected at Day 14 after administration.
Mentions: The recovery of pulmonary inflammation was observed at 14 days after administration. In the SALINE group, inflammatory infiltration in the alveolar septum recovered to normal lung architecture in mice exposed to 10 µg of ZnO nanoparticles, while a slight accumulation of inflammatory cells was noted in mice exposed to 20 µg of ZnO nanoparticles. In contrast, mild inflammation was evident in all mice of the BLM groups after exposure to ZnO nanoparticles (Figure 5 and Figure S1A). To check pulmonary fibrosis, Masson’s trichrome staining and alpha smooth muscle actin (α-SMA) immunohistochemistry were conducted using samples harvested on Day 14. It turns out that exposure to ZnO nanoparticles up to 20 µg had no obvious effects on collagen deposition or fibroblast proliferation, both in the SALINE and BLM groups (data not shown).

Bottom Line: Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important.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 Article: PubMed Central - PubMed

Affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. wendyvvri@med.nagoya-u.ac.jp.

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.

Show MeSH
Related in: MedlinePlus