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.
Richards
I M
IM
Upjohn Company, Kalamazoo, MI 49001.
Griffin
R L
RL
Fidler
S F
SF
Jacobsen
E J
EJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity*; D010996:Pleural Effusion; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D011281:Pregnatrienes; C074965:U 74389F; D010100:Oxygen