Effects of N-Acetylcysteine in Ozone-Induced Chronic Obstructive Pulmonary Disease Model |
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Authors: | Feng Li Cornelis Wiegman Joanna M Seiffert Jie Zhu Colin Clarke Yan Chang Pank Bhavsar Ian Adcock Junfeng Zhang Xin Zhou Kian Fan Chung |
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Institution: | 1. Experimental Studies Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.; 2. Department of Respiratory Medicine, the Affiliated First People’s Hospital of Shanghai Jiao Tong University, Shanghai, P.R. China.; 3. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America .; University of California San Francisco, United States of America, |
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Abstract: | IntroductionChronic 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.MethodsMice 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.ResultsAfter 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 (FEV25/FVC, FEV50/FVC). Mean linear intercept (Lm) 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.ConclusionEmphysema 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. |
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