Antioxidant Enzymes in the Lung

When O₂ is breathed at concentrations between 0.5 and 2.5 atmospheres absolute (ata) for prolonged periods, pulmonary damage is the usual cause of death. ¹ All mammals appear to be susceptible, although the dose response relationship varies with age and species. Exposure of an adult rat to 1 ata O₂ results in death of at least 50% of the animals in 72 hr; ¹ however, rats can adapt to hyperoxia if they are first exposed to 0.8 to 0.9 ata O₂ for several days prior to exposure to pure oxygen. ² In addition, it has recently been shown that administration of bacterial endotoxin can protect rats against hyperoxia without preexposure. ³ Increases in antioxidant enzymes in the lung of rats correlate with adaptation to 1 ata O₂ by either preexposure to hyperoxia ^{4 , 5} or simultaneous exposure to endotoxin. ³ A correlation between the ability to increase antioxidant enzymes and survival in 1 ata O₂ has also been shown by comparison of young and old animals from several species. ⁶ To further test the relationship between antioxidant enzymes and protection against hyperoxia, several studies have investigated whether decreased antioxidant activity correlates with decreased survival in hyperoxia. Both inhibition of Cu-Zn SOD ^{7 , 8} and depletion of glutathione peroxidase ^{9 , 10} caused decreased tolerance of rats to hyperoxia. Nevertheless, studies of whole lung enzyme activities are complicated in interpretation by the significant alteration in lung architecture that accompanies oxygen exposure. ^{2 , 11}