Newborn Mice Lacking the Gene for Cyp1a1 Are More Susceptible to Oxygen-Mediated Lung Injury, and Are Rescued by Postnatal β-Naphthoflavone Administration: Implications for Bronchopulmonary Dysplasia in Premature Infants

Maturu, Paramahamsa; Wei-Liang, Yanhong; Jiang, Weiwu; Wang, Lihua; Lingappan, Krithika; Barrios, Roberto; Liang, Yan; Moorthy, Bhagavatula; Couroucli, Xanthi I.

doi:10.1093/toxsci/kfx036

Cited by 24 publications

(23 citation statements)

References 52 publications

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“…Transgenic mice expressing the human 13.2 Kb CYP1A1 promoter to drive luciferase expression ( CYP1A1 -Luc) on CD-1 background were obtained from Xenogen Corporation (Alameda, CA) [30–32]. Newborn wild type (WT) (CD-1) or CYP1A1 -Luc mice were placed in plexiglass chambers within 12 h of birth, and were either maintained in room air or were exposed to hyperoxia (85% O 2 ) for 7 or 14 days [29,33]. Details of hyperoxia exposures were as reported previously [29].…”

Section: Methodsmentioning

confidence: 99%

“…Newborn wild type (WT) (CD-1) or CYP1A1 -Luc mice were placed in plexiglass chambers within 12 h of birth, and were either maintained in room air or were exposed to hyperoxia (85% O 2 ) for 7 or 14 days [29,33]. Details of hyperoxia exposures were as reported previously [29]. The dams were rotated between room air and hyperoxia-exposed litters every 24 h to prevent oxygen toxicity in the dams.…”

Section: Methodsmentioning

confidence: 99%

“…Pretreatment of rats [25,26] with inducers of CYP1A enzymes attenuates hyperoxic lung injury. Also, adult mice lacking Cyp1a1 [27], or 1a2 [28], and newborn mice deficient in Cyp1a1 [29] are more susceptible to lung injury by hyperoxia, compared to similarly exposed wild type (WT) mice. The mechanisms of induction of human CYP1A1 by hyperoxia are not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Jiang

Maturu

Liang

et al. 2018

Biochemical and Biophysical Research Communications

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Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this study, we tested the hypothesis that newborn transgenic mice carrying the human CYP1A1-Luc promoter will display transcriptional activation of the human CYP1A1 promoter in vivo upon exposure to hyperoxia, and that these mice will be less susceptible to hyperoxic lung injury and alveolar simplification than similarly exposed wild type (WT) mice. Newborn WT (CD-1) or transgenic mice carrying a 13.2 kb human CYP1A1 promoter and the luciferase (Luc) reporter gene (CYP1A1-luc) were maintained in room air or exposed to hyperoxia (85% O) for 7-14 days. Hyperoxia exposure of CYP1A1-Luc mice for 7 and 14 days resulted in 4- and 30-fold increases, respectively, in hepatic Luc (CYP1A1) expression, compared to room air controls. In lung, hyperoxia caused a 2-fold induction of reporter Luc at 7 days, but the induction declined after 14 days. The newborn CYP1A1-Luc mice were less susceptible to lung injury and alveolar simplification than similarly exposed wild type (WT) CD-1 mice. Also, the CYP1A1-Luc mice showed increased levels of hepatic and pulmonary CYP1A1 expression and hepatic CYP1A2 activity after hyperoxia exposure. Hyperoxia also increased NADP(H) quinone reductase (NQO1) pulmonary gene expression in both CD-1 and CYP1A1-Luc mice at both time points, but this was more pronounced in the latter at 14 days. Our results support the hypothesis that hyperoxia activates the human CYP1A1 promoter in newborn mice, and that increased endogenous expression of CYP1A1 and NADP(H) quinone reductase (NQO1) contributes to the decreased susceptibilities to hyperoxic lung injury in the transgenic animals. This is the first report providing evidence of hyperoxia-mediated transcriptional activation of the human CYP1A1 promoter in newborn mice, and this in conjunction with decreased lung injury, suggests that these phenomena have important implications for BPD.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Jiang

Maturu

Liang

et al. 2018

Biochemical and Biophysical Research Communications

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“…Male sex is an independent risk factor for developing BPD (14,19,31,32,68) and in animal models of BPD (33) (51)(52)(53)(54)57). However, sex-specific differences associated with longterm outcomes on completion of alveolarization of the lung remain poorly understood.…”

Section: T Birthmentioning

confidence: 99%

“…Sex also is an important biological parameter for preterm infants who develop BPD because males have worse mortality and morbidities (14,19,31,32,68), including worse neurodevelopmental outcomes at 30 mo postnatal age (76). Smallanimal models of BPD likewise indicate worse outcomes for males than for females (33,(51)(52)(53)(54)57). However, pathogenic mechanisms contributing to sex-specific long-term outcomes remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age

Dahl

Bowen

Aoki

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model using former preterm lambs to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former preterm lambs. Results are compared to term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 months (4M:4F) or 5 months (4M:6F) corrected postnatal age (cPNA) compared to unventilated, age-matched term control lambs (4M:4F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 years and ~6 years, respectively. Multivariable linear regression results showed that former preterm lambs at 2 or 5 months cPNA had significantly thicker distal airspace walls (p<0.001 and p<0.009, respectively), lower volume density of secondary septa (p<0.007 and p<0.001, respectively), and lower radial alveolar count (p<0.003 and p<0.020, respectively) compared to term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former preterm lambs. This new model provides opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.

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Recent progress in neonatal hyperoxic lung injury

Rao,

Zhou,

Chen

et al. 2024

Pediatric Pulmonology

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With the progress in neonatal intensive care, there has been an increase in the survival rates of premature infants. However, this has also led to an increased incidence of neonatal hyperoxia lung injury and bronchopulmonary dysplasia (BPD), whose pathogenesis is believed to be influenced by various prenatal and postnatal factors, although the exact mechanisms remain unclear. Recent studies suggest that multiple mechanisms might be involved in neonatal hyperoxic lung injury and BPD, with sex also possibly playing an important role, and numerous drugs have been proposed and shown promise for improving the treatment outcomes of hyperoxic lung injury. Therefore, this paper aims to analyze and summarize sex differences in neonatal hyperoxic lung injury, potential pathogenesis and treatment progress to provide new ideas for basic and clinical research in this field.

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Newborn Mice Lacking the Gene for Cyp1a1 Are More Susceptible to Oxygen-Mediated Lung Injury, and Are Rescued by Postnatal β-Naphthoflavone Administration: Implications for Bronchopulmonary Dysplasia in Premature Infants

Cited by 24 publications

References 52 publications

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age

Recent progress in neonatal hyperoxic lung injury

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