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.