Premature rats treated with propylthiouracil show enhanced pulmonary antioxidant enzyme gene expression and improved survival during prolonged exposure to hyperoxia.
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)
D000818:Animals; D000831:Animals, Newborn; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010544:Peroxidases / Q000378:metabolism*; D011247:Pregnancy; D011441:Propylthiouracil / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*; D015996:Survival Rate
D011663:Pulmonary Surfactants; D011441:Propylthiouracil; D010544:Peroxidases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase