AN AGE-RELATED DIFFERENCE IN HYPEROXIA LETHALITY - ROLE OF LUNG ANTIOXIDANT DEFENSE-MECHANISMS

The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were res istant while mature animals were sensitive. Antioxidant enzymes increa sed during the oxygen exposure in neonatal but not in mature rats, sug gesting they were important in the age-related toxicity difference. Be cause no studies had compared the response of mature and old rats to h yperoxia, we exposed Fischer 344 rats, aged 2 and 27 mo, to > 98% oxyg en. Unexpectedly, the old rats lived significantly longer than young, 114 and 65 h, respectively No histopathological differences were found to explain the results. Of the antioxidants, only glutathione peroxid ase (GPx) activity was higher in the lungs of nonexposed old rats. Sup eroxide dismutase (SOD) was higher in the young, results opposite thos e expected if SOD was important in the lethality difference. No antiox idant induction occurred in the old oxygen-exposed rats. These results suggest that although there may be a role for GPx, mechanisms in addi tion to antioxidant protection and inflammation are likely responsible for the age-related difference in hyperoxia lethality.