Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 277; no. 2pt; pp. L423 - L429
• Main Authors: Thebaud, B, Tibboel, D, Rambaud, C, Mercier, J.C, Bourbon, J.R, Dinh-Xuan, A.T, Archer, S.L
• Format: Journal Article
• Language: English
• Published: United States 01.08.1999
• Subjects: Animals; Body Weight; DNA - metabolism; Female; Herbicides; Hernia, Diaphragmatic - chemically induced; Hernia, Diaphragmatic - physiopathology; Hernia, Diaphragmatic - prevention & control; Hernias, Diaphragmatic, Congenital; Incidence; Lung - growth & development; Lung - pathology; Organ Size; Phenyl Ethers; Pregnancy; Prenatal Exposure Delayed Effects; Proteins - metabolism; Rats; Rats, Sprague-Dawley; retinoic acid; Survival Analysis; Vitamin A - pharmacology
• ISSN: 0002-9513; 1040-0605; 2163-5773; 1522-1504
• DOI: 10.1152/ajplung.1999.277.2.l423

1  Réanimation Néonatale and 4  Service d'Anatomo-Pathologie, Hôpital Antoine Béclère, 92141 Clamart; 2  Service de Physiologie, Hôpital Cochin, Université René Descartes, 75679 Paris Cedex 14; 5  Réanimation Pédiatrique, Hôpital Robert Debré, 75019 Paris; 6  Institut National de la Sante et de la Recherche Médicale Unité 319, Université Paris 7, 75251 Paris, France; 3  Pediatric Surgery, Sophia Children's Hospital, 3015 Rotterdam, The Netherlands; and 7  Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2B7 Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia often limits survival. Vitamin A (Vit A) is an important signal for lung growth. We hypothesized that antenatal treatment with Vit A would stimulate lung growth and decrease mortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2,4-dichlorophenyl- p -nitrophenyl ether). Nitrofen was administered to pregnant rats on day 12  of gestation (term 22 days). Rats were assigned to five groups: three groups received one dose of oral antenatal Vit A (15,000 IU) before ( day 10 ), concomitant with ( day 12 ), or after ( day 14 ) nitrofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in all groups receiving Vit A ( day 10 , 44%; day 12 , 20%; and day 14 , 40%) compared with the nitrofen-treated group (84%; P  < 0.05). The 72-h survival was higher in all 3 Vit A-treated groups ( day 10 , 40%; day 12 , 58%; and day 14 , 70%) compared with the nitrofen-treated group (16%; P  < 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vit A lowers the incidence and severity of experimental CDH and increases lung growth and maturation. lung hypoplasia; lung development; retinoic acid; persistent pulmonary hypertension of the newborn; pulmonary circulation