Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia.
Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex+TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitro-phenylether (Nitrofen) on gestational day 10. Dex+TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients.
Ijsselstijn
H
H
Department of Pediatric Surgery, Erasmus University Rotterdam, The Netherlands.
Pacheco
B A
BA
Albert
A
A
Sluiter
W
W
Donahoe
P K
PK
De Jongste
J C
JC
Schnitzer
J J
JJ
Tibboel
D
D
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008170:Lung Compliance / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity; D010647:Phenyl Ethers / Q000633:toxicity; D011030:Pneumothorax / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D010575:Pesticides; D010647:Phenyl Ethers; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D004247:DNA; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; C007350:nitrofen