Prenatal dexamethasone administration to premature rats exposed to prolonged hyperoxia: a new rat model of pulmonary fibrosis (bronchopulmonary dysplasia).
OBJECTIVE
To evaluate the postnatal effects of prenatal dexamethasone treatment of preterm rats and to test the hypothesis that prenatal dexamethasone treatment projects against pulmonary oxygen toxicity in the preterm rats and stimulates lung antioxidant enzyme levels in response to hyperoxia.


METHODS
We administered dexamethasone (0.4 mg/kg, intraperitoneally), or equivolume saline solution to pregnant rats at 48 and 24 hours before premature delivery at gestation day 21. Both groups of prematurely delivered rat pups were randomly assigned to other > 95% O2 or room air immediately after birth and brief resuscitation.


RESULTS
The hyperoxic survival rates from day 1 through day 14 were similar in both dexamethasone-treated and control preterm O2 groups. At 7 days of hyperoxia, the preterm pups demonstrated similar lung antioxidant enzyme activity and sufactant content responses to high O2 in the dexamethasone-treated and control groups. Lung quantitative morphometry changes were similar (equal degree of inhibition of normal alveolar development) in both groups. Unexpectedly, the lungs of the preterm O2 control rats showed evidence of septal fibrosis and the pups that received dexamethasone-O2 showed even greater severity of septal fibrosis and a greater increase (+50%) of lung hydroxyproline compared with the O2 groups control rats.


CONCLUSIONS
In preterm animals, prenatal dexamethasone administration does not show any of the hypothesized protective effects against hyperoxia or protective biochemical lung changes during prolonged O2 exposure. However, prenatal dexamethasone administration with prolonged exposure of the preterm rat to hyperoxia results in a pulmonary pathologic picture quite similar to bronchopulmonary dysplasia.
Chen
Y
Y
Department of Pediatrics, University of Miami School of Medicine, FL 33101, USA.
Martinez
M A
MA
Frank
L
L
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D001997:Bronchopulmonary Dysplasia / Q000473:pathology* / Q000517:prevention & control; D002374:Catalase / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010100:Oxygen / Q000633:toxicity*; D011247:Pregnancy; D011658:Pulmonary Fibrosis / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D005938:Glucocorticoids; D003907:Dexamethasone; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010100:Oxygen