Supplemental
oxygen is frequently used in the treatment of infants having pulmonary insufficiency, but prolonged
hyperoxia may contribute to the development of
bronchopulmonary dysplasia in these infants.
Cytochrome P4501A
enzymes have been implicated in hyperoxic
lung injury.
Retinoic acid (RA) plays a key role in lung development. Here, we tested the hypotheses that newborn rats exposed to a combination of RA and
hyperoxia would be less susceptible to
lung injury than those exposed to
hyperoxia only and that modulation of CYP1A
enzymes by RA contribute to the beneficial effects of RA against hyperoxic
lung injury. Newborn rats exposed to
hyperoxia for 7 days showed higher lung
weight/body weight ratios compared with those exposed to RA +
hyperoxia.
Hyperoxia for 7 days also caused a significant increase in hepatic and pulmonary
CYP1A1/1A2 expression compared with air-breathing controls. RA +
hyperoxia treatment lowered the expression of these genes. Seven to 30 days after withdrawal of
hyperoxia, the animals showed marked induction of hepatic and pulmonary
CYP1A1/1A2 expression, but animals that had been given RA +
hyperoxia displayed lower expression of these
enzymes. On postnatal days 22 or 38, the hyperoxic animals displayed retarded lung alveolarization; however, the RA +
hyperoxia-exposed animals showed improved alveolarization. The improved alveolarization in animals given RA +
hyperoxia, in conjunction with the attenuation of
CYP1A1 and 1A2 expression in these animals, suggests that this phenomenon may play a role in the beneficial effects of RA.