TY - JOUR
T1 - Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene
AU - Thakur, Vijay S.
AU - Liang, Yanhong W.
AU - Lingappan, Krithika
AU - Jiang, Weiwu
AU - Wang, Lihua
AU - Barrios, Roberto
AU - Zhou, Guodong
AU - Guntupalli, Bharath
AU - Shivanna, Binoy
AU - Maturu, Paramahamsa
AU - Welty, Stephen E.
AU - Moorthy, Bhagavatula
AU - Couroucli, Xanthi I.
N1 - Funding Information:
This research was supported in part supported by RO1 Grants HL-088343 to X.C., and ES-009132, HL-087174, ES-019689, and HL-112516 to B.M. 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 Mr. Edward Felix of the M.D. Anderson Cancer Center in the carrying out LC–MS/MS analyses for determination of 8-iso-PGF 2α levels.
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2014/10/5
Y1 - 2014/10/5
N2 - Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25mg/kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn rats were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon.
AB - Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25mg/kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn rats were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon.
KW - Alveolar simplification
KW - Cytochrome P4501A1/1A2/1B1
KW - Hyperoxic lung injury
KW - Maternal benzo[a]pyrene
KW - Newborn rat
KW - Oxidative stress
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U2 - 10.1016/j.toxlet.2014.03.006
DO - 10.1016/j.toxlet.2014.03.006
M3 - Article
C2 - 24657529
AN - SCOPUS:84907167579
VL - 230
SP - 322
EP - 332
JO - Toxicology Letters
JF - Toxicology Letters
SN - 0378-4274
IS - 2
ER -