Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of (99m)Tc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6), 2) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to- dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series. In the O2 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 in W/D, BAL/P, and DAS clearance rate were attenuated by U-74389G treatment. Cell accumulation in the O2 alone group was also attenuated by U-74389G treatment. In conclusion, this study suggests that U-74389G attenuates lung injury induced by hyperoxic exposure.
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