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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 254069, 14 pages
http://dx.doi.org/10.1155/2013/254069
Research Article

Exacerbated Airway Toxicity of Environmental Oxidant Ozone in Mice Deficient in Nrf2

1Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
2Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Received 11 January 2013; Accepted 29 March 2013

Academic Editor: Mi-Kyoung Kwak

Copyright © 2013 Hye-Youn Cho et al. 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.

Abstract

Ozone (O3) is a strong oxidant in air pollution that has harmful effects on airways and exacerbates respiratory disorders. The transcription factor Nrf2 protects airways from oxidative stress through antioxidant response element-bearing defense gene induction. The present study was designed to determine the role of Nrf2 in airway toxicity caused by inhaled O3 in mice. For this purpose, Nrf2-deficient ( ) and wild-type ( ) mice received acute and subacute exposures to O3. Lung injury was determined by bronchoalveolar lavage and histopathologic analyses. Oxidation markers and mucus hypersecretion were determined by ELISA, and Nrf2 and its downstream effectors were determined by RT-PCR and/or Western blotting. Acute and sub-acute O3 exposures heightened pulmonary inflammation, edema, and cell death more severely in mice than in mice. O3 caused bronchiolar and terminal bronchiolar proliferation in both genotypes of mice, while the intensity of compensatory epithelial proliferation, bronchial mucous cell hyperplasia, and mucus hypersecretion was greater in mice than in mice. Relative to , O3 augmented lung protein and lipid oxidation more highly in mice. Results suggest that Nrf2 deficiency exacerbates oxidative stress and airway injury caused by the environmental pollutant O3.