PT  - JOURNAL ARTICLE
AU  - Xanthi I. Couroucli
AU  - Yanhong W. Liang
AU  - Weiwu Jiang
AU  - Roberto Barrios
AU  - Bhagavatula Moorthy
TI  - Attenuation of Oxygen-Induced Abnormal Lung Maturation in Rats by Retinoic Acid: Possible Role of Cytochrome P4501A Enzymes
AID  - 10.1124/jpet.105.100677
DP  - 2006 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 946--954
VI  - 317
IP  - 3
4099  - http://jpet.aspetjournals.org/content/317/3/946.short
4100  - http://jpet.aspetjournals.org/content/317/3/946.full
SO  - J Pharmacol Exp Ther2006 Jun 01; 317
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics