Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model.
Chorioamnionitis is a risk factor for the development of bronchopulmonary dysplasia. Endotoxin-induced oxidative stress to the fetus in the uniquely hypoxic intrauterine environment has not been reported. Using a model of chorioamnionitis, we measured markers of pulmonary and systemic oxidant exposures in fetal lambs at 124 d gestation (term = 150 d) exposed to 10 mg intra-amniotic endotoxin 2 d (n = 6) or 7 d (n = 6) before delivery, or saline as controls (n = 9). The 7 d endotoxin-exposed animals had 3-fold higher protein carbonyls (0.66 +/- 0.46 versus 0.23 +/- 0.14 nmol/mg protein) and 10-fold greater myeloperoxidase activity (2.38 +/- 1.87 versus 0.27 +/- 0.18 nM) in the bronchoalveolar lavage fluid (BALF), suggestive of neutrophil-derived oxidant activity. However, in the lung tissue, protein carbonyls, superoxide dismutase, and peroxiredoxin 1 were not different between groups. The expression of peroxiredoxin 1 was prominent, primarily in the peri-bronchiolar epithelium. Notably, evidence of oxidant exposure was minimal at 2 d when BALF inflammatory cells, lung IL-1beta, and IL-8 were highest. Intra-amniotic endotoxin induced systemic oxidative stress as plasma protein carbonyl was elevated at 7 d (0.14 +/- 0.04 nmol/mg protein; p = 0.005). Surfactant protein A and B mRNAs were highest at 2 d, suggesting that oxidative stress did not contribute to the lung maturation response. A modest lung oxidative stress in chorioamnionitis could contribute to bronchopulmonary dysplasia.
Cheah
Fook-Choe
FC
Department of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. fook-choe.cheah@cchmc.org
Jobe
Alan H
AH
Moss
Timothy J
TJ
Newnham
John P
JP
Kallapur
Suhas G
SG
D000653:Amniotic Fluid; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002821:Chorioamnionitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005325:Fetal Organ Maturity; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007267:Injections; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000196:embryology / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D011247:Pregnancy; D050050:Protein Carbonylation; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; C482199:lipopolysaccharide, E coli O55-B5; D054464:Peroxiredoxins; D009195:Peroxidase; D013482:Superoxide Dismutase