Oxygen-induced lung damage. Relationship to lung mitochondrial glutathione levels.
Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen-induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen-induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
L J
LJ
Department of Medicine (Pulmonary Division), Northwestern University Medical School, Chicago, IL 60611.
Anderson
J
J
D000818:Animals; D019328:Buthionine Sulfoximine; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity*
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C042431:S-ethyl glutathione; D005978:Glutathione; D010100:Oxygen