TY - JOUR
T1 - Prenatal administration of the cytochrome P4501A inducer, Β-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice
T2 - Implications for bronchopulmonary dysplasia (BPD) in premature infants
AU - Couroucli, Xanthi I.
AU - Liang, Yan hong Wei
AU - Jiang, Weiwu
AU - Wang, Lihua
AU - Barrios, Roberto
AU - Yang, Peiying
AU - Moorthy, Bhagavatula
N1 - Funding Information:
This work was in part supported by RO1 grants HL-088343 to X.I.C., HL-070921, HL-087174, ES-019689, and ES 009132 to B.M., and American Lung Association grant to X.I.C. The study sponsors had no involvement in study design, data collection, analysis and interpretation, writing of the report or decision to submit the paper for publication. The authors thank Dr. Edward Felix of the M.D. Anderson Cancer Center in the carrying out LC-MS/MS analyses for determination of BNF levels in lung and liver tissues of fetal and newborn mice. We appreciate the assistance of Esther Inman in the preparation of this manuscript.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/10/15
Y1 - 2011/10/15
N2 - 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 (40mg/kg), i.p., once daily for 3days 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 1-5days. After 3-5days 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 24-72h resulted in increased pulmonary levels of the F 2-isoprostane 8-iso-PGF 2-, 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.
AB - 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 (40mg/kg), i.p., once daily for 3days 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 1-5days. After 3-5days 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 24-72h resulted in increased pulmonary levels of the F 2-isoprostane 8-iso-PGF 2-, 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.
KW - Bronchopulmonary dysplasia
KW - CYP1A enzymes
KW - Hyperoxia
KW - Lung injury
KW - Newborn
KW - Oxidant injury
UR - http://www.scopus.com/inward/record.url?scp=80053131956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053131956&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2011.06.018
DO - 10.1016/j.taap.2011.06.018
M3 - Article
C2 - 21745492
AN - SCOPUS:80053131956
VL - 256
SP - 83
EP - 94
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -