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A Catalytic Antioxidant Attenuates Alveolar Structural Remodeling in Bronchopulmonary Dysplasia

Departments of Medicine, National Jewish Medical and Research Center; Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; Department of Pediatrics, University of Texas Health Sciences Center; Southwest Foundation for Biomedical Research, San Antonio, Texas; Department of Pathology, Harvard Medical School; Departments of Pathology, Children's Hospital; and Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Ling-Yi L. Chang, Ph.D., National Jewish Medical and Research Center, 1400 Jackson Street, K708, Denver, CO 80206. E-mail: changl{at}njc.org

Superoxide anion and other oxygen-free radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia. We tested the hypothesis that a catalytic antioxidant metalloporphyrin AEOL 10113 can protect against hyperoxia-induced lung injury using a fetal baboon model of bronchopulmonary dysplasia. Fetal baboons were delivered by hysterotomy at 140 days of gestation (term = 185 days) and given 100% oxygen for 10 days. Morphometric analysis of alveolar structure showed that fetal baboons on 100% oxygen alone had increased parenchymal mast cells and eosinophils, increased alveolar tissue volume and septal thickness, and decreased alveolar surface area compared with animals given oxygen as needed. Treatment with AEOL 10113 (continuous intravenous infusion) during 100% oxygen exposure partially reversed these oxygen-induced changes. Hyperoxia increased the number of neuroendocrine cells in the peripheral lung, which was preceded by increased levels of urine bombesin-like peptide at 48 hours of age. AEOL 10113 inhibited the hyperoxia-induced increases in urine bombesin-like peptide and numbers of neuroendocrine cells. An increasing trend in oxygenation index over time was observed in the 100% oxygen group but not the mimetic-treated group. These results suggest that AEOL 10113 might reduce the risk of pulmonary oxygen toxicity in prematurely born infants.

Key Words: metalloporphyrin • morphometry • bombesin-like peptide • neuroendocrine cells

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