Abstract
Prolonged exposure to hyperoxia markedly inhibits normal lung development (alveolarization and respiratory surface area expansion) in immature animals. Since (a) hyperoxia results in excess hydroxyl radical (OH ⋅) formation, (b) (OH ⋅) is implicated in O 2-induced lipid peroxidation and DNA alterations, and (c) both OH ⋅ formation and its interaction with DNA are Fe ++ dependent; chelation of Fe ++ should act to protect against pulmonary O 2 toxicity and hyperoxic inhibition of lung development. We therefore treated litters of newborn rats with the iron chelator Deferoxamine mesylate (DES) (150 mg/kg/day) during a 10-day exposure to >95% O 2. Morphometric analysis demonstrated that compared to the mean airspace size in air control rat pups ( L m = 44.5 μm hyperoxic exposure resulted in a 34% larger mean air space diameter in O 2-saline rat lungs (59.5 μm) versus only an 11% enlargement in O 2-DES lungs (51.1 μ ∗). Lung internal surface area (cm 2) per 100-g body weight were air control = 4480, O 2- saline = 3750 (↓ 20.3%), and O 2-DES = 4125 ∗ (↓ 7.9%) ( ∗p<0.05 versus O 2-saline group ) . DES-treated animals also had significantly decreased lung conjugated diene levels during hyperoxic exposure and increased lung elastin content (reflective of preserved lung alveolar formation) compared to O 2-saline rats. These results indicate that DES treatment substantially ameliorated the inhibitory effects of neonatal hyperoxic exposure on normal lung development.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have