title: Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia.
abstract: OBJECTIVE
  Nitrofen induces heart hypoplasia together with congenital diaphragmatic hernia (CDH) in rats. Intracellular oxidative stress might be one of the mechanisms of action of the teratogen, and vitamin A has been shown to reverse in part these effects when administered simultaneously or shortly after it. This study aims at testing the hypothesis that vitamin A and other antioxidant vitamins, such as E and C, could improve myocardial development even when administered late in gestation, a likely useful period for prenatal medication.
  
  
  METHODS
  Time-mated Sprague-Dawley female rats were exposed to either vehicle (control) or 100 mg of nitrofen (experimental) on day 9.5 of gestation. In 3 additional groups, the animals were exposed to vitamin A (total 15000 IU), vitamin E (total 150 IU), or vitamin C (total 150 IU) on days 16, 17, and 18. The fetuses were recovered on day 21, and randomly selected hearts of those with CDH were processed for histologic studies (hematoxylin-eosin and periodic acid-Schiff stainings), DNA and protein contents, and ki-67 (proliferation) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (apoptosis) studies. The differences among groups were assessed by analysis of variance with Bonferroni/Dunn post hoc tests and a threshold of significance of P < .05.
  
  
  RESULTS
  Nitrofen induced heart hypoplasia in terms of decreased heart/body weight, cell mass (less DNA and protein), and proportion of proliferating cells with increased apoptosis. Vitamin C alleviated weight hypoplasia and the 3 vitamins were able to restore cell mass and to reestablish near-normal figures of proliferation and apoptosis.
  
  
  CONCLUSIONS
  Antioxidant vitamins A, E, and C given late in gestation alleviate heart hypoplasia that accompanies CDH in the rat model. This timing suggests that the beneficial effects are exerted on the maturational phase of development.
authors.affiliation: Department of Pediatric Surgery, Research Laboratory, Hospital Universitario La Paz, 28046 Madrid, Spain.
authors.forename: Salomé
authors.initials: S
authors.lastname: González-Reyes
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Martínez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Tovar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005318:Fetal Heart / Q000002:abnormalities / Q000187:drug effects; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000188:drug therapy*; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital; D020287:In Situ Nick-End Labeling; D016877:Oxidants / Q000494:pharmacology / Q000627:therapeutic use*; D010647:Phenyl Ethers; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens; D014801:Vitamin A / Q000494:pharmacology / Q000627:therapeutic use; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016877:Oxidants; D010647:Phenyl Ethers; D013723:Teratogens; D014815:Vitamins; D014801:Vitamin A; D014810:Vitamin E; D004247:DNA; C007350:nitrofen; D001205:Ascorbic Acid