Inhalation Exposure to Zinc Oxide Nanoparticle Induced Allergic Airway Inflammation in Mice
Date Issued
2015
Date
2015
Author(s)
Tiunn, Hong-Lun
Abstract
Introduction Zinc oxide nanoparticles (ZnO NPs) have been widely utilized in cosmetics, sunscreens, semiconductors, and solar panels. Previous research found mice had developed an allergic airway inflammation (AAI) after ZnO NPs exposure via oropharyngeal aspiration and an allergic adjuvant effect had be detected when ZnO NPs co-exposed to an allergen. Current permissible exposure level (PEL) of zinc fume set by TWOSHA is 5 mg/m3, but there was no PEL specific for ZnO NPs. In the present study, we focused on two effects caused by ZnO NPs: the first is the AAI; and the second is the allergic adjuvant effect. In order to explore the relationship between inhaled ZnO NPs exposure and AAI, we used half of the PEL of zinc fume as exposure dose. In the allergic adjuvant effect experiment, we used 30% of PEL of zinc fume as exposure dose and OVA as an allergen to reveal the possible allergic adjuvant effect caused by ZnO NPs. Method 7-weeks old female C57BL/6J mice were used in this study. ZnO NPs which used in this study was made by nanoparticle generator. The study contained two parts, the AAI experiment and the adjuvant experiment. In AAI experiment, animals were randomly divided into two groups: the ZnO NPs group and the control group. Animals were sacrificed at day 1, day 3 and 1 week after exposure. In the adjuvant experiment, animals were randomly separated into four groups: ZnO NPs, OVA, ZnO NPs+OVA and control. Animals were sacrificed at day 1 after exposure. Bronchoalveolar lavage fluid (BALF) was collected for total cell count, cell differential count, biomarkers and cytokines measurement. Result Diameter of ZnO NPs was 60.6 nm in AAI experiment and 61.1 nm in adjuvant experiment. Diameter of ZnO NPs between two experiments did not show significant difference. Mass concentration measured by filter weighting was 2.5 mg/m3 in AAI experiment and 1.5 mg/m3 in adjuvant experiment. In AAI experiment, total cell count significantly increased at day 1, and slightly increased at day 3 and 1 week after exposure. Neutrophil count shared same trend with total cell count. Eosinophil count increased in all time points, but decreased rapidly at day 3 and 1 week after exposure. IL-5, IL-13, TNF-α and IFN-γ significantly increased at day 1 after exposure. In adjuvant experiment, total cell count significantly increased in OVA+ZnO NPs group and ZnO NPs group, but there was not significantly different between two groups. Eosinophil was not detected in any exposure group. Results of Cytokine levels of ZnO NPs group shown that IL-5, IL-13, TNF-α and IFN-γ significantly increased. Discussion In AAI experiment, observation of eosinophil recruitments and IL-5 increase confirmed 2.5 mg/m3 ZnO NPs exposure caused AAI. Also, the rapid decrease of eosinophil count indicated AAI recovered after exposure source was removed. In adjuvant experiment, eosinophil was not detected in the ZnO NPs group or the OVA+ZnO NPs group, but the level of IL-5 increased in both two groups. These indicated 1.5 mg/m3 of ZnO NPs failed to recruit eosinophils in BALF, but it still triggered an AAI-related pathway and increased level of cytokines. Conclusion Inhaled ZnO NPs exposure induced AAI even in relatively low doses compared to PEL of zinc fume. Up to date, there is still no regulation for nanomaterial in occupational health. PEL of ZnO NPs is necessary to set up in order to protect workers’ health. Moreover, the dose-response relation and the mechanism of ZnO NPs-induced AAI are not fully revealed by the scientific society yet. Further research will be essential to reveal these problems. Keywords: Zinc oxide nanoparticle, eosinophil, allergic airway inflammation
Subjects
zinc oxide nanoparticle
eosinophil
allergic airway inflammation
Type
thesis
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