Supplemental
oxygen, frequently used in premature infants, has been implicated in the development of
bronchopulmonary dysplasia (BPD). While the mechanisms of
oxygen-induced
lung injury are not known,
reactive oxygen species (ROS) are most likely involved in the process. Here, we tested the hypothesis that upregulation of
cytochrome P450 (CYP) 1A
isoforms in lung and liver may lead to protection against hyperoxic
lung injury. Adult male Sprague-Dawley rats were pretreated with the CYP1A inducer
beta-naphthoflavone (beta-NF) (80 mg/kg/day), once daily for 4 days, followed by exposure to hyperoxic environment (O2 > 95%) or room air (normoxia) for 60 h.
Pleural effusions were measured as estimates of
lung injury. Activities of hepatic and pulmonary
CYP1A1 were determined by measurement of
ethoxyresorufin O-deethylation (
EROD) activity. Northern hybridization and Western blot analysis of lung and liver were performed to assess
mRNA and
protein levels, respectively. Our results showed that beta-NF-treated animals, which displayed the highest pulmonary and hepatic induction in
EROD activity (10-fold and 8-fold increase over
corn oil (CO) controls, respectively), offered the most protective effect against hyperoxic
lung injury, p < 0.05. Northern and Western blot analysis correlated well with
enzyme activities. Our results showed an inverse correlation between pulmonary and hepatic CYP1A expression and the extent of
lung injury, which supports the hypothesis that CYP1A
enzyme plays a protective role against
oxygen-mediated tissue damage.