title: Effects of N-acetylcysteine in ozone-induced chronic obstructive pulmonary disease model.
abstract: BACKGROUND
  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 (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Experimental Studies Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom ; Department of Respiratory Medicine, the Affiliated First People's Hospital of Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Cornelis
authors.initials: C
authors.lastname: Wiegman
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Seiffert
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Colin
authors.initials: C
authors.lastname: Clarke
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.forename: Pank
authors.initials: P
authors.lastname: Bhavsar
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004646:Emphysema / Q000473:pathology; D005100:Expectorants / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D010126:Ozone / Q000009:adverse effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D012129:Respiratory Function Tests
chemical_list: D005100:Expectorants; D008315:Malondialdehyde; D010126:Ozone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000111:Acetylcysteine