Open AccessEffects of N-Acetylcysteine in Ozone-Induced Chronic Obstructive Pulmonary Disease Model
Author(s) -
Feng Li,
Coen Wiegman,
Joanna Seiffert,
Jie Zhu,
Colin Clarke,
Yan Chang,
PK Bhavsar,
Ian M. Adcock,
Jim Zhang,
Xin Zhou,
Kian Fan Chung
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0080782
Subject(s) - acetylcysteine , vital capacity , medicine , pulmonary function testing , lung volumes , pulmonary compliance , lung , copd , inflammation , functional residual capacity , pharmacology , inhalation , oxidative stress , anesthesia , immunology , antioxidant , chemistry , lung function , diffusing capacity , biochemistry
Chronic exposure to high levels of ozone induces emphysema and chronic inflammation in mice. We determined the recovery from ozone-induced injury and whether an antioxidant, N-acetylcysteine (NAC), could prevent or reverse the lung damage. Methods Mice were exposed to ozone (2.5 ppm, 3 hours/12 exposures, over 6 weeks) and studied 24 hours (24h) or 6 weeks (6W) later. Nac (100 mg/kg, intraperitoneally) was administered either before each exposure (preventive) or after completion of exposure (therapeutic) for 6 weeks. Results After ozone exposure, there was an increase in functional residual capacity, total lung volume, and lung compliance, and a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV 25 /FVC, FEV 50 /FVC). Mean linear intercept (L m ) and airway hyperresponsiveness (AHR) to acetylcholine increased, and remained unchanged at 6W after cessation of exposure. Preventive NAC reduced the number of BAL macrophages and airway smooth muscle (ASM) mass. Therapeutic NAC reversed AHR, and reduced ASM mass and apoptotic cells. Conclusion Emphysema and lung function changes were irreversible up to 6W after cessation of ozone exposure, and were not reversed by NAC. The beneficial effects of therapeutic NAC may be restricted to the ASM.