Oral N-acetylcysteine reduces bleomycin-induced collagen deposition in the lungs of mice.
N-acetylcysteine (NAC) has been employed in the treatment of acute lung injury but its therapeutic value is as yet unproven. In the present study we examined the effect of both L- and D-forms of NAC as inhibitors of bleomycin-induced fibrosis in mice. We hypothesized that, because of the D-form is not metabolized, it may be more effective than the L-form in ameliorating lung injury and fibrosis. Both drugs were given daily in the drinking water at a dose of approximately 400 mg.kg-1 body weight commencing one week prior to a single intratracheal instillation of bleomycin at a dose of 6 mg.kg-1 body weight. Lung injury was assessed 35 days later by measuring total lung collagen content, lung wet weight and examination of tissues by light and electron microscopy. Total collagen content and lung wet weight of animals receiving bleomycin together with L-NAC were 2.90 +/- 0.03 mg and 0.23 +/- 0.01 g, respectively. The values for collagen content, but not wet weight, were significantly less (p less than 0.05) than those given for bleomycin alone (3.90 +/- 0.02 mg and 0.260 +/- 0.005 g, respectively), but greater than (p less than 0.05) controls (2.10 +/- 0.01 mg and 0.160 +/- 0.002 g, respectively). Values for collagen content and wet weight of animals given bleomycin together with D-NAC (3.10 +/- 0.02 mg and 0.21 +/- 0.01 mg, respectively) were both significantly greater than values for control animals but lower than animals given bleomycin alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Shahzeidi
S
S
Dept of Thoracic Medicine, National Heart and Lung Institute, University of London, UK.
Sarnstrand
B
B
Jeffery
P K
PK
McAnulty
R J
RJ
Laurent
G J
GJ
D000111:Acetylcysteine / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001761:Bleomycin; D003094:Collagen / Q000032:analysis*; D008168:Lung / Q000737:chemistry* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D001761:Bleomycin; D003094:Collagen; D000111:Acetylcysteine