Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities.
We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.
Sluiter
W
W
Department of Biochemistry I, Eramus University, Rotterdam, The Netherlands.
Bos
A P
AP
Silveri
F
F
Tenbrinck
R
R
Kraakslee
R
R
Tibboel
D
D
Koster
J F
JF
Molenaar
J C
JC
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity; D006548:Hernia, Diaphragmatic / Q000139:chemically induced*; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D010647:Phenyl Ethers / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D006540:Herbicides; D010647:Phenyl Ethers; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C007350:nitrofen