Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model

Fook-Choe Cheah, Alan Jobe, Timothy Moss, John Newnham, Suhas Kallapur

Research output: Contribution to journalArticleResearchpeer-review

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-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.
Original languageEnglish
Pages (from-to)274 - 279
Number of pages6
JournalPediatric Research
Volume63
Issue number3
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this

Cheah, Fook-Choe ; Jobe, Alan ; Moss, Timothy ; Newnham, John ; Kallapur, Suhas. / Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model. In: Pediatric Research. 2008 ; Vol. 63, No. 3. pp. 274 - 279.
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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-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.",
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Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model. / Cheah, Fook-Choe; Jobe, Alan; Moss, Timothy; Newnham, John; Kallapur, Suhas.

In: Pediatric Research, Vol. 63, No. 3, 2008, p. 274 - 279.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model

AU - Cheah, Fook-Choe

AU - Jobe, Alan

AU - Moss, Timothy

AU - Newnham, John

AU - Kallapur, Suhas

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/18091343

U2 - 10.1203/PDR.0b013e31815f653b

DO - 10.1203/PDR.0b013e31815f653b

M3 - Article

VL - 63

SP - 274

EP - 279

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 3

ER -