Effect of in vivo hyperoxia on the glutathione system in neonatal rat lung

Relative resistance to oxygen toxicity in newborn animals of some species has been associated with a rapid increase in antioxidants in lung tissue homogenate. This study investigated the effect of hyperoxia on the glutathione system antioxidants in lung tissue of neonatal rats exposed to hyperoxia for 15 days. Neonatal rats were exposed to either 100% oxygen or air for 0, 3, 6, 9, 12, and 15 days prior to sacrifice for determination of glutathione and the glutathione system antioxidant enzymes in whole lung homogenate. There were significantly higher levels of total glutathione at 3, 6, and 9 days and of reduced glutathione at 3 and 6 days in oxygen-exposed animals compared to air-exposed controls. These differences were no longer present after 12 or 15 days of exposure to hyperoxia. Glutathione peroxidase and glucose-6-phosphate dehydrogenase remained higher in lung tissue from oxygen-exposed animals from 6 through 12 days of hyperoxia. The failure to maintain sustained high levels of total glutathione during hyperoxia might suggest that glutathione depletion is a factor in the timing of death from oxygen toxicity in these animals. The absence of a sustained increase in oxidized glutathione disulfide is more consistent with other explanations for this transient increase in total glutathione.