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

Background/Aim: 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 useftil period for prenatal medication. Material and 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 2 1, and randomly selected hearts of those with CDH were processed for histologic studies (hernatoxylin-cosin 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. (c) 2005 Elsevier Inc. All rights reserved.