Effect of the 21-aminosteroid U74389G on oxygen-induced free radical production, lipid peroxidation, and inhibition of lung growth in neonatal rats

• Published in: Pediatric research Vol. 46; no. 2; pp. 215 - 223
• Main Authors: XIAOPING LUO, SEDLACKOVA, L, BELCASTRO, R, CABACUNGAN, J, LYE, S. J, TANSWELL, A. K
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.08.1999
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Animals, Newborn; Antioxidants - pharmacology; Biological and medical sciences; Bronchopulmonary Dysplasia - metabolism; Bronchopulmonary Dysplasia - prevention & control; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Free Radicals - metabolism; Humans; Infant, Newborn; Intensive care medicine; Lipid Peroxidation - drug effects; Lung - drug effects; Lung - growth & development; Lung - metabolism; Medical sciences; Oxygen - metabolism; Oxygen - pharmacology; Pregnatrienes - pharmacology; Rats; Rats, Sprague-Dawley; Premature; Lung disease; Oxygen; Rat; Respiratory disease; Rodentia; Antioxidant; Radical scavenger; Free radical; Prevention; Newborn diseases; Vertebrata; Mammalia; Newborn animal; Bronchus disease; Bronchopulmonary dysplasia; Peroxidation
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-199908000-00015

Bronchopulmonary dysplasia is a chronic pneumopathy of preterm infants, with significant associated mortality and morbidity, for which there is no effective preventive therapy. Pulmonary O2 toxicity is thought to be a major contributor to the development of bronchopulmonary dysplasia, and antioxidant interventions hold significant promise for therapy. The relative importance of specific reactive oxygen species in the development of O2-mediated lung injury is unknown. In this study, we tested the effect of a synthetic 21-aminosteroid, U74389G, on 95% O2-induced free radical production, lipid peroxidation, and inhibition of postnatal lung growth in a neonatal rat model. Lipid peroxidation products, as measured by total 8-isoprostane and aldehydes, and hydroxyl radical formation, assessed using salicylate metabolites, in rat lungs and serum were significantly increased after exposure to 95% O2. These changes could be completely or partially attenuated by U74389G. However, U74389G did not improve the survival rate or lung wet-to-dry weight ratio. Expression of proliferating cell nuclear antigen, a marker for DNA synthesis, was examined by immunohistochemistry. Four- or 7-d-old control rat lungs had active DNA synthesis, which was inhibited by exposure to 95% O2. U74389G had a protective effect against 95% O2-mediated inhibition of DNA synthesis. Air-exposed animals treated with U74389G had a modest reduction in lung DNA synthesis, consistent with a role for hydroxyl radicals or lipid hydroperoxides as second messengers in the normal regulation of lung growth.