EFFECT OF THE 21-AMINOSTEROID, U-74389F, ON HYPEROXIC LUNG INJURY IN RATS

Hyperoxia (> 95 % oxygen) in rats caused an increase in lung weight an d 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 t he 21-aminosteroid U-74389F, 3, 10, and 30 mg/kg twice daily throughou t oxygen exposure, produced 8, 42, and 18% inhibition of the oxygen-in duced increase in lung weight, respectively. However, U-74389F did not inhibit the hyperoxia-induced accumulation of neutrophils in bronchoa lveolar lavage fluid. No pleural fluid could be aspirated from the tho rax of air-breathing controls. The volume of pleural fluid in oxygen-e xposed, 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.