Abstract
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-1β, 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.
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Abbreviations
- BALF:
-
bronchoalveolar lavage fluid
- BPD:
-
bronchopulmonary dysplasia
- CAM:
-
chorioamnionitis
- LPS:
-
lipopolysaccharide
- MPO:
-
myeloperoxidase
- Prx 1:
-
peroxiredoxin 1
- ROS:
-
reactive oxygen species
- Sat PC:
-
saturated phosphatidylcholine
- SOD:
-
superoxide dismutase
- SP-:
-
surfactant protein
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Acknowledgements
The authors thank Dr. Machiko Ikegami for the surfactant analyses of samples, and Mr. Dave Loudy of Morphologic Core, Cincinnati Children's Research Foundation, for imaging assistance. We also thank Mr. Tim Harwood, Dr. Alexander Peskin, and Professor Christine Winterbourn of the Free Radical Research Group, Christchurch School of Medicine and Health Sciences, New Zealand, for their technical advice.
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Supported by National Institutes of Health grants HD 12714 and HL 65397.
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Cheah, FC., Jobe, A., Moss, T. et al. Oxidative Stress in Fetal Lambs Exposed to Intra-amniotic Endotoxin in a Chorioamnionitis Model. Pediatr Res 63, 274–279 (2008). https://doi.org/10.1203/PDR.0b013e31815f653b
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DOI: https://doi.org/10.1203/PDR.0b013e31815f653b
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