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.
Beckman
David L
DL
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834 , USA.
Cummings
James J
JJ
Katwa
Laxmansa C
LC
Whitehurst
Marvin E
ME
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D019587:Dietary Supplements; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects; D006548:Hernia, Diaphragmatic / Q000150:complications; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000209:etiology / Q000517:prevention & control; D010575:Pesticides / Q000633:toxicity*; D010647:Phenyl Ethers / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage*
D000975:Antioxidants; D010575:Pesticides; D010647:Phenyl Ethers; D014810:Vitamin E; C007350:nitrofen