Premature rats treated with propylthiouracil show enhanced pulmonary antioxidant enzyme gene expression and improved survival during prolonged exposure to hyperoxia.

Abstract

In full-term newborn rats, propylthiouracil (PTU) treatment has been previously shown to decrease susceptibility to O2-induced lung damage and improve survival during hyperoxic exposure. However, no differences were found in lung antioxidant enzyme (AOE) activity responses to hyperoxia compared with O2-exposed untreated (control) term rats. To further explore possible pulmonary protective effects of PTU treatment in prematurely delivered animals, we administered PTU (0.015%) in drinking water to timed-pregnant rats for the final 10 d of gestation prior to delivery 1 d before term, and during lactation; control pregnant/nursing rats received untreated water. Both groups of 21-d premature rat pups were randomized to either > 95% O2 or room air exposure after birth for up to 14 d. The left lungs of 7-d exposure pups were used to quantitate the concentrations of AOE mRNA by solution hybridization; the right lungs of the same pups were assayed for AOE activities. PTU treatment resulted in survival rates of O2-exposed preterm rat pups that were consistently higher at all time periods in hyperoxia including 7 d [PTU, 67 of 82 (82%) versus control pups, 58 of 113 (51%); p < 0.001] and 14 d [PTU, 31 of 39 (79%) versus control, 15 of 66 (23%); p < 0.001]. Further evidence of increased tolerance to > 95% O2 in PTU pups included a significant decrease in the incidence of microscopic intraalveolar edema and a significant increase in lung tissue surfactant-related phospholipids compared with O2-exposed control pups.(ABSTRACT TRUNCATED AT 250 WORDS)