ATTENUATION OF HYPEROXIC LUNG INJURY BY THE 21-AMINOSTEROID U-74389G

Hyperoxic lung injury is attributable to oxygen radicals produced unde r hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a poten t antioxidant. We examined the effect of U-74389G on lung injury in gu inea pigs during exposure to 90% O-2, for 48 h. We injected either veh icle or 10 mg/kg of U-74389G 30 min before the O-2 exposure and inject ed the same dose 12, 24, and 36 h later. We performed two series of ex periments after exposure. In the first series, we measured the clearan ce rate of Tc-99m-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups con sisting of 1) control (n = 6), 2) O-2 alone (n = 6), and 3) O-2 + AS ( n = 6). In the second series, pulmonary endothelial injury was estimat ed by using 28 guinea pigs divided into four experimental groups consi sting of 1) control (n = 8), 2) AS alone (n = 5), 3) O-2 alone (n = 6) , and 4) O-2 + AS (n = 9). In the second series, we measured the wet-t o-dry weight ratio (W/D) as an index of lung water and the concentrati on ratio of I-125-labeled albumin in lung tissue and bronchoalveolar l avage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) a s indexes of pulmonary endothelial damage. Cell accumulation in BAL fl uid and lung tissue samples was also assessed in the second series. In the O-2 alone group, W/D, T/P, BAL/P, and DAS clearance rate were all increased compared with the control group (P < 0.05). The increases i n W/D, BAL/P, and DAS clearance rate were attenuated by U-74389G treat ment. Cell accumulation in the O-2 alone group was also attenuated by U-74389G treatment. In conclusion, this study suggests that U-74389G a ttenuates lung injury induced by hyperoxic exposure.