Can maternal vitamin e supplementation prevent lung hypoplasia in the nitrofen-induced rat model of congenital diaphragmatic hernia?

Recent studies suggest a role for antioxidants in the prevention of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH). We studied the effects of vitamin E in the nitrofen-rat model of CDH. After an initial fast, timed-pregnant Sprague-Dawley rats were gavage-fed nitrofen at gestational day 11 (term is 22 d). On the same day, one group was given a s.c. injection of vitamin E in alcohol; a second group was given an injection of alcohol alone. A third group received no treatment (control). Fetuses were delivered on day 21, and static pressure-volume curves were measured by immersion. Lungs were analyzed for total DNA and protein content by standard methods. A total of 203 fetuses were studied. Of 151 nitrofen-exposed fetuses, 77% had CDH; 92% of these were right-sided. CDH was present in 82% of vehicle-treated fetuses and 71% of vitamin E-treated fetuses (p=0.17). Nitrofen-exposed fetuses not only were smaller than control fetuses but also had disproportionately smaller lungs and poorer lung function, even when CDH was absent; however, lung function was worse when CDH was present. Vitamin E treatment did not improve either lung growth or function, although there was a trend toward less CDH. We have shown, for the first time, that the lung hypoplasia seen in nitrofen-exposed rat fetuses is associated with a dramatic reduction in static lung function, even when CDH is not present. Finally, our findings support the notion that lung hypoplasia in the nitrofen-rat model is independent of CDH formation.