Effect of the 21-aminosteroid, U-74389F, on hyperoxic lung injury in rats.

Hyperoxia (> 95% oxygen) in rats caused an increase in lung weight and an accumulation of fluid in the thorax. The mean lung wet weight of air-breathing controls at 60 h was 1.2 +/- 0.01 g, and that of vehicle-treated, oxygen-exposed animals was 2.45 +/- 0.05 g. Treatment with the 21-aminosteroid U-74389F, 3, 10, and 30 mg/kg twice daily throughout oxygen exposure, produced 8, 42, and 18% inhibition of the oxygen-induced increase in lung weight, respectively. However, U-74389F did not inhibit the hyperoxia-induced accumulation of neutrophils in bronchoalveolar lavage fluid. No pleural fluid could be aspirated from the thorax of air-breathing controls. The volume of pleural fluid in oxygen-exposed, vehicle-treated animals and animals treated with 3, 10, and 30 mg/kg U-74389F b.i.d. was 6.5 +/- 0.9, 2.6 +/- 0.6, 0.8 +/- 0.3, and 1.3 +/- 0.5 ml, respectively. U-74389F or its biologs are of potential value for the treatment of lung diseases in which oxidant damage has been implicated.