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ToxSci Advance Access published online on June 15, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi226
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received April 1, 2005
Accepted June 3, 2005

Respiratory Toxicology

Attenuation of Hyperoxic Lung Injury by the CYP1A Inducer {beta}-Naphthoflavone

Anuj Sinha 1, Kathirvel Muthiah 1, Weiwu Jiang 1, Xanthi Couroucli 1, Roberto Barrios 2, and Bhagavatula Moorthy 1*

1 Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030
2 Department of Pathology, The Methodist Hospital, Houston, TX 77030

* To whom correspondence should be addressed.
Bhagavatula Moorthy, E-mail: Bmoorthy{at}bcm.tmc.edu


  Abstract

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 pre-treated with the CYP1A inducer beta-naphthoflavone ({beta}-NF) (80 mg/kg/day), once daily for four days, followed by exposure to hyperoxic environment (O2 > 95%) or room air (normoxia) for 60 hours. 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.

Keywords: Hyperoxia; Cytochrome P450; Beta-naphthoflavone.
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