Journal
NANOTOXICOLOGY
Volume 9, Issue 1, Pages 43-53Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2014.886740
Keywords
Inflammation; inhalation; nanoparticles; systemic effect; zinc oxide
Categories
Funding
- Center of Nanomedicine Research at the National Health Research Institutes, Taiwan [NM-101-PP-07, NM-101-PP-08]
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Inhalation of zinc oxide nanoparticles (ZnONP) has potential health impact. Because zinc ion may involve in the toxicity of ZnONP, we compared adverse effects of inhaled aerosolized ZnONP and zinc nitrate in mice. Aerosolized ZnONP and zinc nitrate were well-dispersed in the inhalation chamber. Inhalation of 0.86 mg/m(3) ZnONP or 1.98 mg/m(3) zinc nitrate for 5 h caused acute inflammation mainly at bronchioloalveolar junctions of lungs at 24-h post-exposure. Inhalation of ZnONP or zinc nitrate increased metallothionein expression in the epithelial cells of brochioloalveolar junction. While the effects on cytokines secretion in bronchoalveolar lavage were similar between ZnONP and zinc nitrate, only ZnONP increased lactate dehydrogenase activity. However, repeated exposure to 0.86 mg/m(3) ZnONP 5 h/day for 5 days failed to cause a similar adverse effect. Either single or repeated exposure to 0.86 mg/m(3) ZnONP increased activities of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and creatine phosphokinase in blood. In contrast, exposure to zinc nitrate had no similar systemic effects. In human bronchial epithelial cells, ZnONP-induced interleukin-8 secretion was partially prevented by co-treatment with the Toll-like receptor 4 (TLR4) inhibitor. Furthermore, ZnONP-induced pulmonary inflammation was greater in wild-type mice than in TLR4-deficent mice. It appears that ZnONP-induced acute pulmonary inflammation partially depended on TLR4. In summary, we demonstrated the dose-responsive effects for inhalation of ZnONP and zinc nitrate in mice. The threshold of cytokines induction for inhalation of ZnONP for 5 h was 0.43 mg/m(3). The particulate characters of ZnONP might contribute to the systemic adverse effects and shall be evaluated for assessing its health impact in humans.
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