This Article Full Text Full Text (PDF) Online Supplement Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chang, L.-Y. L. Articles by Crapo, J. D. Search for Related Content PubMed PubMed Citation Articles by Chang, L.-Y. L. Articles by Crapo, J. D.

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

This article has been cited by other articles:

				D. C. McCurnin, R. A. Pierce, B. C. Willis, L. Y. Chang, B. A. Yoder, I. S. Yuhanna, P. L. Ballard, R. I. Clyman, N. Waleh, W. Maniscalco, et al. Postnatal Estradiol Up-regulates Lung Nitric Oxide Synthases and Improves Lung Function in Bronchopulmonary Dysplasia Am. J. Respir. Crit. Care Med., March 15, 2009; 179(6): 492 - 500. [Abstract] [Full Text] [PDF]

				A. Y. MAKINDE, X. LUO-OWEN, A. RIZVI, J. D. CRAPO, R. D. PEARLSTEIN, J. M. SLATER, and D. S. GRIDLEY Effect of a Metalloporphyrin Antioxidant (MnTE-2-PyP) on the Response of a Mouse Prostate Cancer Model to Radiation Anticancer Res, January 1, 2009; 29(1): 107 - 118. [Abstract] [Full Text] [PDF]

				K. Bry Newborn Resuscitation and the Lung NeoReviews, November 1, 2008; 9(11): e506 - e512. [Abstract] [Full Text] [PDF]

				D. McCurnin, S. Seidner, L.-Y. Chang, N. Waleh, M. Ikegami, J. Petershack, B. Yoder, L. Giavedoni, K. H. Albertine, M. J. Dahl, et al. Ibuprofen-Induced Patent Ductus Arteriosus Closure: Physiologic, Histologic, and Biochemical Effects on the Premature Lung Pediatrics, May 1, 2008; 121(5): 945 - 956. [Abstract] [Full Text] [PDF]

				K. Bry, J. A. Whitsett, and U. Lappalainen IL-1beta Disrupts Postnatal Lung Morphogenesis in the Mouse Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 32 - 42. [Abstract] [Full Text] [PDF]

				C. Avivi-Green, M. Singal, and W. F. Vogel Discoidin Domain Receptor 1-deficient Mice Are Resistant to Bleomycin-induced Lung Fibrosis Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 420 - 427. [Abstract] [Full Text] [PDF]

				M. T. Ganter and J.-F. Pittet Bombesin-like Peptides: Modulators of Inflammation in Acute Lung Injury? Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 1 - 2. [Full Text] [PDF]

				S. Padela, J. Cabacungan, S. Shek, R. Belcastro, M. Yi, R. P. Jankov, and A. K. Tanswell Hepatocyte Growth Factor Is Required for Alveologenesis in the Neonatal Rat Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 907 - 914. [Abstract] [Full Text] [PDF]

				J. P. Kinsella, T. A. Parker, J. M. Davis, and S. H. Abman Superoxide Dismutase Improves Gas Exchange and Pulmonary Hemodynamics in Premature Lambs Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 745 - 749. [Abstract] [Full Text] [PDF]

				P. J. Barnes New approaches to COPD Eur. Respir. Rev., September 1, 2005; 14(94): 2 - 11. [Abstract] [Full Text] [PDF]

				V L Kinnula Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases Thorax, August 1, 2005; 60(8): 693 - 700. [Abstract] [Full Text] [PDF]

				T. Rangasamy, J. Guo, W. A. Mitzner, J. Roman, A. Singh, A. D. Fryer, M. Yamamoto, T. W. Kensler, R. M. Tuder, S. N. Georas, et al. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice J. Exp. Med., July 5, 2005; 202(1): 47 - 59. [Abstract] [Full Text] [PDF]

				D. C. McCurnin, R. A. Pierce, L. Y. Chang, L. L. Gibson, S. Osborne-Lawrence, B. A. Yoder, J. D. Kerecman, K. H. Albertine, V. T. Winter, J. J. Coalson, et al. Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L450 - L459. [Abstract] [Full Text] [PDF]

				M. Yi, R. P. Jankov, R. Belcastro, D. Humes, I. Copland, S. Shek, N. B. Sweezey, M. Post, K. H. Albertine, R. L. Auten, et al. Opposing Effects of 60% Oxygen and Neutrophil Influx on Alveologenesis in the Neonatal Rat Am. J. Respir. Crit. Care Med., December 1, 2004; 170(11): 1188 - 1196. [Abstract] [Full Text] [PDF]

				R. Kaarteenaho-Wiik and V. L. Kinnula Distribution of Antioxidant Enzymes in Developing Human Lung, Respiratory Distress Syndrome, and Bronchopulmonary Dysplasia J. Histochem. Cytochem., September 1, 2004; 52(9): 1231 - 1240. [Abstract] [Full Text] [PDF]

				M. J. Tobin Pediatrics, Surfactant, and Cystic Fibrosis in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 277 - 287. [Full Text] [PDF]

				J.D. Crapo Oxidative stress as an initiator of cytokine release and cell damage Eur. Respir. J., September 20, 2003; 22(44_suppl): 4s - 6s. [Full Text] [PDF]

				M. Subramaniam, K. Sugiyama, D. H. Coy, Y. Kong, Y. E. Miller, P. F. Weller, K. Wada, E. Wada, and M. E. Sunday Bombesin-like Peptides and Mast Cell Responses: Relevance to Bronchopulmonary Dysplasia? Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 601 - 611. [Abstract] [Full Text] [PDF]

				Y. Li and J. M. Davis Delivering antioxidants by zip code Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L281 - L282. [Full Text] [PDF]

				V. L. Kinnula and J. D. Crapo Superoxide Dismutases in the Lung and Human Lung Diseases Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1600 - 1619. [Abstract] [Full Text] [PDF]

				A. K. Tanswell and R. P. Jankov Bronchopulmonary Dysplasia: One Disease or Two? Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 1 - 2. [Full Text] [PDF]