Attenuation of hyperoxic lung injury by the CYP1A inducer beta-naphthoflavone.
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.
Sinha
Anuj
A
Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Muthiah
Kathirvel
K
Jiang
Weiwu
W
Couroucli
Xanthi
X
Barrios
Roberto
R
Moorthy
Bhagavatula
B
D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000209:etiology*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000502:physiology*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D018496:Hyperoxia / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2