The fate of antioxidant enzymes in bronchoalveolar lavage fluid over 7 days in mice with acute lung injury
Sciuto, A.M.; Cascio, M.B.; Moran, T.S.; Forster, J.S.
Inhalation Toxicology 15(7): 675-685
ISSN/ISBN: 0895-8378 PMID: 12754689 DOI: 10.1080/08958370390197245
Characterization of lung injury is important if timely therapeutic intervention is to be used properly and successfully. In this study, lung injury was defined as the progressive formation of pulmonary edema. Our model gas was phosgene, a pulmonary edemagenic compound. Phosgene, widely used in industry, can produce life-threatening pulmonary edema within hours of exposure. Four groups of 40 CD-1 male mice were exposed whole-body to either air or a concentration x time (c x t) amount of 32-42 mg/m(3) (8-11 ppm) phosgene for 20 min (640-840 mg x min/m(3)). Groups of air- or phosgene-exposed mice were euthanized 1, 4, 8, 12, 24, 48, or 72 h or 7 days postexposure. The trachea was excised, and 800 micro l saline was instilled into the lungs and washed back and forth 5 times to collect bronchoalveolar lavage fluid (BALF). The antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), total glutathione (GSH), and protein were determined at each time point. Phosgene exposure significantly enhanced both GPx and GR in phosgene-exposed mice compared with air-exposed mice from 4 to 72 h, p < or = 0.01 and p < or = 0.005, respectively. BALF GSH was also significantly increased, p < or = 0.01, from 4 to 24 h after exposure, in comparison with air-exposed. BALF protein, an indicator of air/blood barrier integrity, was significantly higher than in air-exposed mice 4 h to 7 days after exposure. In contrast, BALF SOD was reduced by phosgene exposure from 4 to 24 h, p < or = 0.01, versus air-exposed mice. Except for protein, all parameters returned to control levels by 7 days postexposure. These data indicate that the lung has the capacity to repair itself within 24-48 h after exposure by reestablishing a functional GSH redox system despite increased protein leakage. SOD reduction during increased leakage may indicate that barrier integrity is affected by superoxide anion production.