Is there a role for antioxidants in prevention of pulmonary hypoplasia in nitrofen-induced rat model of congenital diaphragmatic hernia?
OBJECTIVE
Many studies suggest a role for antioxidants in the prevention of lung hypoplasia in nitrofen-induced rat models with congenital diaphragmatic hernia (CDH). This study investigates the oxidative status and the histological outcome of prenatal administration of vitamins E and C with synergistic effect, and effect of N-acetylcysteine (NAC) to improve lung maturation of nitrofen-induced rats.


METHODS
CDH was induced by maternal administration of a single oral dose of nitrofen on day 9.5 of gestation, and the Sprague-Dawley rats were randomly divided into five groups: nitrofen (N), nitrofen + vitamin C (NC), nitrofen + vitamin E (NE), nitrofen + vitamin C + vitamin E (NCE) and nitrofen + NAC (NNAC). A control group in which only vehicle was administered was included. Cesarean section was performed on day 21. Body weight (BW) and total lung weight (LW) of all fetuses with CDH were recorded; lung histological evaluation was performed, and protein content of lungs, determination of thiobarbituric acid reactive substances, and the protein carbonyls in tissue samples were determined.


RESULTS
A total of 133 rat fetuses with CDH were investigated. The body weight and the lung weight of fetuses of all groups that were exposed to nitrofen were significantly decreased than of the control group (P < 0.05). The animals exposed to nitrofen with different antioxidants showed increased protein levels in lung tissue. However, in the NCE and the NNAC groups, protein levels were significantly increased than in the others. Malondialdehyde levels significantly decreased in the NCE and the NNAC groups when compared with the NC and the NE groups. In addition, the NCE and NNAC groups decreased protein oxidation to control levels, and no significant difference was observed between control and these two antioxidants groups. The N, NC, NE and NNAC groups showed minimal improvement in lung histology; the NCE groups showed the most improvement in lung histology when compared with the other nitrofen plus antioxidant groups.


CONCLUSIONS
Prenatal administration of NAC and vitamin E in combination with vitamin C represented the best effects to avoid oxidative damage and protein content of the lungs in rat pups with CDH at birth.
Cigdem
Murat Kemal
MK
Department of Pediatric Surgery, Medical School, Dicle University, 21280, Diyarbakir, Turkey. mkcigdem@hotmail.com
Kizil
Goksel
G
Onen
Abdurrahman
A
Kizil
Murat
M
Nergiz
Yusuf
Y
Celik
Yusuf
Y
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D005333:Fetus / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000150:complications*; D065630:Hernias, Diaphragmatic, Congenital; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008171:Lung Diseases / Q000517:prevention & control*; D008297:Male; D008431:Maternal-Fetal Exchange; D010575:Pesticides; D010647:Phenyl Ethers / Q000008:administration & dosage; D011247:Pregnancy; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D016166:Free Radical Scavengers; D010575:Pesticides; D010647:Phenyl Ethers; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; C007350:nitrofen; D001205:Ascorbic Acid; D000111:Acetylcysteine