Abstract

Inhaled zinc oxide nanoparticles (ZnONPs) have high deposition rates in the alveolar region of the lungs; however, the adverse health effects of ZnONPs on the respiratory system are unclear. Herein, pathobiological responses of the respiratory system of mice that received intratracheal administration of ZnONPs were investigated by a combination of molecular and imaging (SPECT and CT) approaches. Also, normal BEAS-2B and adenocarcinoma A549 cells were used to confirm the results in mice. First, female BALB/c mice were administrated a series of doses of 20-nm ZnONPs and were compared to the phosphate-buffered saline control for 24-h and 28-day follow-up observations. Field emission-scanning electron microscopy and an energy-dispersive X-ray microanalysis were first used to characterize ZnONPs. After 24 h, instilled ZnONPs had caused significant increases in lactic dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), caspase-3, and the p63 tumor marker in lung tissues (p < 0.05). Airway inflammation was present in a dose-dependent manner from the upper to the lower airway as analyzed by SPECT. After 28 days, p63 had significantly increased due to ZnONP exposure in lung tissues (p < 0.05). Pulmonary inflammatory infiltration mainly occurred in the left and right subsegments of the secondary bronchial bifurcation as observed by CT. A significant increase in p63 and decrease in TTF1 levels were observed in BEAS-2B cells by ZnONP (p < 0.05), but not in A549 cells. Our results demonstrated that regional lung inflammation occurred with ZnONP exposure. We also showed that p63 was consistently overexpressed due to ZnONP exposure in vivo and in vitro. This work provides unique findings on the p63 response and the pathobiology in response to ZnONPs, which could be important to the study of pulmonary toxicity and repair.

Original languageEnglish
Pages (from-to)13-22
Number of pages10
JournalToxicology and Applied Pharmacology
Volume327
DOIs
Publication statusPublished - Jul 15 2017

Fingerprint

Zinc Oxide
Nanoparticles
Lung
Respiratory system
Respiratory System
Tissue
Electron Probe Microanalysis
Molecular Imaging
Bronchoalveolar Lavage Fluid
Tumor Biomarkers
Single-Photon Emission-Computed Tomography
Deposition rates
Infiltration
Caspase 3
Field emission
Electron Scanning Microscopy
Toxicity
Pneumonia
Oxidoreductases
Milk

Keywords

  • Inflammation
  • Nanoparticle
  • Oxidative stress
  • Thyroid transcription factor-1
  • Tumor protein p63

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Pulmonary pathobiology induced by zinc oxide nanoparticles in mice : A 24-hour and 28-day follow-up study. / Chuang, Hsiao Chi; Chuang, Kai Jen; Chen, Jen Kun; Hua, His En; Shen, Yen Ling; Liao, Wei Neng; Lee, Chii Hong; Pan, Chih Hong; Chen, Kuan Yuan; Lee, Kang Yun; Hsiao, Ta Chih; Cheng, Tsun Jen.

In: Toxicology and Applied Pharmacology, Vol. 327, 15.07.2017, p. 13-22.

Research output: Contribution to journalArticle

Chuang, Hsiao Chi ; Chuang, Kai Jen ; Chen, Jen Kun ; Hua, His En ; Shen, Yen Ling ; Liao, Wei Neng ; Lee, Chii Hong ; Pan, Chih Hong ; Chen, Kuan Yuan ; Lee, Kang Yun ; Hsiao, Ta Chih ; Cheng, Tsun Jen. / Pulmonary pathobiology induced by zinc oxide nanoparticles in mice : A 24-hour and 28-day follow-up study. In: Toxicology and Applied Pharmacology. 2017 ; Vol. 327. pp. 13-22.
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AU - Hua, His En

AU - Shen, Yen Ling

AU - Liao, Wei Neng

AU - Lee, Chii Hong

AU - Pan, Chih Hong

AU - Chen, Kuan Yuan

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AU - Hsiao, Ta Chih

AU - Cheng, Tsun Jen

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