Oxygen-induced lung damage: Relationship to lung mitochondrial glutathione levels

Lewis J Smith*, J. Anderson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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. The absence of a relationship between mitochondrial GSH levels and susceptibility to oxygen-induced lung damage, plus the capacity of lung mitochondria to maintain the GSH content when that of the cytoplasm is reduced and to increase GSH content rapidly and to a greater extent than the cytoplasm during hyperoxic exposure, indicate that mitochondrial GSH levels do not determine susceptibility to hyperoxic lung damage.

Original languageEnglish (US)
Pages (from-to)1452-1457
Number of pages6
JournalAmerican Review of Respiratory Disease
Volume146
Issue number6
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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