Administration of bovine superoxide dismutase fails to prevent chronic pulmonary sequelae of neonatal oxygen exposure in the rat.
Using a rat model, we assessed the efficacy of varying doses of superoxide dismutase of (SOD) to affect plasma and tissue SOD concentrations and to attenuate dysplastic changes of lung and pulmonary vascular growth, which are chronic sequelae of neonatal oxygen exposure. One hundred forty-three 1-day-old Sprague-Dawley rats were divided into two groups and exposed to hyperoxia (0.96 to 1.0 Fio2) or room air for 8 postnatal days. Each group was subdivided into five treatment groups, which received 6, 20, 100, or 200 mg/kg/d SOD or a placebo, intramuscularly every 12 hours. All rats were then placed in room air; 52 were killed, and lung tissue and blood samples were obtained for measurement of bovine SOD concentration. The remaining rats received routine care until 58 to 60 days of age, when functional and morphologic cardiopulmonary changes were assessed. Bovine SOD concentration of pooled plasma samples increased 26-fold, from 2 to 50 micrograms/mL, between the 6 and 200 mg/kg/d SOD groups, but mean tissue concentration increased only six-fold, from 0.34 to 2.1 micrograms/lung. Cardiovascular and pulmonary changes found in each oxygen group, regardless of SOD dosage, included elevated right ventricular pressure, increased right ventricular weight, decreased number of small pulmonary arteries/mm2, decreased number of alveoli/mm2, and increased volume proportion of lung parenchyma. Thus, high plasma concentrations of bovine SOD failed to prevent the chronic cardiovascular and pulmonary sequelae of neonatal oxygen exposure in the rat, possibly because SOD did not reach the intracellular sites of action.
D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007231:Infant, Newborn; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000254:growth & development; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000378:metabolism; D013997:Time Factors
D013482:Superoxide Dismutase; D010100:Oxygen