Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G.
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 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tasaka
S
S
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ishizaka
A
A
Urano
T
T
Sayama
K
K
Sakamaki
F
F
Nakamura
H
H
Terashima
T
T
Waki
Y
Y
Soejima
K
K
Fujishima
S
S
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004727:Endothelium / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D015633:Extravascular Lung Water / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D010100:Oxygen / Q000633:toxicity*; D011281:Pregnatrienes / Q000627:therapeutic use*; D012711:Serum Albumin, Radio-Iodinated; D013213:Starch / Q000031:analogs & derivatives; D017556:Technetium Compounds
D000975:Antioxidants; D011281:Pregnatrienes; D012711:Serum Albumin, Radio-Iodinated; D017556:Technetium Compounds; C074965:U 74389F; D013213:Starch; C012880:dialdehyde starch; D010100:Oxygen