title: Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure.
abstract: BACKGROUND
  The number of Clara cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.
  
  
  METHODS
  Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS + NAC group) oral intake of NAC 80 mg x kg(-1) x d(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The mRNA expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.
  
  
  RESULTS
  Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3 +/- 14.7 vs. 53.7 +/- 11.5, P < 0.05). The Clara cell particles in cytoplasm decreased in the CS group (P < 0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8 +/- 4.3 and 29.5 +/- 2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1 +/- 3.8 and 43.8 +/- 5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P < 0.05). No significant difference was observed in GSH level ((181 +/- 26) nmol/L in the control group vs. (170 +/- 18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1 +/- 17.5) decreased (P < 0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213 +/- 40) nmol/L vs. (170 +/- 18) nmol/L in the CS group) increased too (P < 0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1 +/- 6.4 and 34.3 +/- 6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P > 0.05). No significant difference was found in the expression of CC16 mRNA among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r = -0.592, P < 0.05), but not with GSH level.
  
  
  CONCLUSIONS
  One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.
authors.affiliation: Department of Respiratory Medicine, Peking University First Hospital, Beijing 100034, China.
authors.forename: Ji-ping
authors.initials: JP
authors.lastname: Liao
authors.forename: Chun-hua
authors.initials: CH
authors.lastname: Chi
authors.forename: Hai-chao
authors.initials: HC
authors.lastname: Li
authors.forename: Xiu-ying
authors.initials: XY
authors.lastname: Tang
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism*; D000818:Animals; D055745:Bronchioles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005470:Fluorometry; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D011897:Random Allocation; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014598:Uteroglobin; D005978:Glutathione; D000111:Acetylcysteine