Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia

• Published in: Journal of pediatric surgery Vol. 40; no. 8; pp. 1269 - 1274
• Main Authors: González-Reyes, Salomé, Martínez, Leopoldo, Tovar, Juan A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2005
• Subjects: Animals; Apoptosis - drug effects; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Disease Models, Animal; DNA - analysis; Female; Fetal Heart - abnormalities; Fetal Heart - drug effects; Heart Defects, Congenital - chemically induced; Heart Defects, Congenital - drug therapy; Hernia, Diaphragmatic - chemically induced; Hernias, Diaphragmatic, Congenital; In Situ Nick-End Labeling; Oxidants - pharmacology; Oxidants - therapeutic use; Phenyl Ethers; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Teratogens; Vitamin A - pharmacology; Vitamin A - therapeutic use; Vitamin E - pharmacology; Vitamin E - therapeutic use; Vitamins - pharmacology; Vitamins - therapeutic use; Antioxidants; Vitamin A; Congenital diaphragmatic hernia; Heart hypoplasia; Rat; Vitamin E; Vitamin C; Oxidation; Nitrofen
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2005.05.009

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. 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 15 000 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. 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. 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.