title: Prenatal administration of the cytochrome P4501A inducer, Β-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: implications for bronchopulmonary dysplasia (BPD) in premature infants.
abstract: Supplemental oxygen contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this investigation, we tested the hypothesis that prenatal treatment of pregnant mice (C57BL/6J) with the cytochrome P450 (CYP)1A1 inducer, ß-napthoflavone (BNF), will lead to attenuation of lung injury in newborns (delivered from these dams) exposed to hyperoxia by mechanisms entailing transplacental induction of hepatic and pulmonary CYP1A enzymes. Pregnant mice were administered the vehicle corn oil (CO) or BNF (40 mg/kg), i.p., once daily for 3 days on gestational days (17-19), and newborns delivered from the mothers were either maintained in room air or exposed to hyperoxia (>95% O(2)) for 1-5 days. After 3-5 days of hyperoxia, the lungs of CO-treated mice showed neutrophil infiltration, pulmonary edema, and perivascular inflammation. On the other hand, BNF-pretreated neonatal mice showed decreased susceptibility to hyperoxic lung injury. These mice displayed marked induction of ethoxyresorufin O-deethylase (EROD) (CYP1A1) and methoxyresorufin O-demethylase (MROD) (CYP1A2) activities, and levels of the corresponding apoproteins and mRNA levels until PND 3 in liver, while CYP1A1 expression alone was augmented in the lung. Prenatal BNF did not significantly alter gene expression of pulmonary NAD(P)H quinone reductase (NQO1). Hyperoxia for 24-72 h resulted in increased pulmonary levels of the F(2)-isoprostane 8-iso-PGF(2α), whose levels were decreased in mice prenatally exposed to BNF. In conclusion, our results suggest that prenatal BNF protects newborns against hyperoxic lung injury, presumably by detoxification of lipid hydroperoxides by CYP1A enzymes, a phenomenon that has implications for prevention of BPD in infants.
authors: Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. xanthic@bcm.edu
authors: Xanthi I
authors: XI
authors: Couroucli
authors: Yan-hong Wei
authors: YH
authors: Liang
authors: Weiwu
authors: W
authors: Jiang
authors: Lihua
authors: L
authors: Wang
authors: Roberto
authors: R
authors: Barrios
authors: Peiying
authors: P
authors: Yang
authors: Bhagavatula
authors: B
authors: Moorthy
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000517:prevention & control*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D018496:Hyperoxia / Q000188:drug therapy*; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019324:beta-Naphthoflavone / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1