POLYCYCLIC AROMATIC HYDROCARBONS: ULTRASENSITIVE DETECTION, EARLY LIFE EXPOSURES-CLINICAL OUTCOMES (PRETERM BIRTHS, CHRONIC LUNG DISEASE, AND NEUROCOGNITIVE DEFICITS), PREVENTION AND REMEDIATION
多环芳烃:超灵敏检测、生命早期暴露-临床结果(早产、慢性肺病和神经认知缺陷)、预防和补救
基本信息
- 批准号:10382017
- 负责人:
- 金额:$ 1.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-28 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcidsAdultAdult Respiratory Distress SyndromeAirAlveolarAnimalsAromatic Polycyclic HydrocarbonsAttenuatedBenzo(a)pyreneBronchopulmonary DysplasiaChronic lung diseaseClinicalCollaborationsCombined Modality TherapyCorn OilDetectionDoseEpoxide hydrolaseExposure toGlycolsGoalsHyperoxiaLaboratoriesLinoleic AcidsLungMaternal ExposureMeasuresMusNeurocognitive DeficitNewborn InfantOralOutcomeOxygenPregnancyPremature BirthPremature InfantPreventionPulmonary Valve InsufficiencyResearch TrainingRiskTestingUreaVisitWild Type MouseWomancytokineearly life exposureenvironmental chemicalexperienceexposed human populationexternshipinhibitor/antagonistleukotoxinlung injurynovel markerpostnatalpregnantprenatal exposureremediationsuperfund site
项目摘要
Project Summary
The major objective of this project is to provide research and training experience to Dr. Guobin Xia as a
KC Donnelly Externship trainee. He will visit Dr. Bruce Hammock’s laboratory at UC Davis for his externship.
Supplemental oxygen is frequently given to preterm infants and adults with pulmonary insufficiency, but
hyperoxia contributes to lung injury, which in turn leads to bronchopulmonary dysplasia (BPD) in preterm
infants and ARDS in adults. Environmental chemicals such as polycyclic aromatic hydrocarbons (PAHs),
which are present in Superfund sites are known to increase the risk of preterm birth (PTB) in women living near
Superfund sites. In this project, Dr. Guobin Xia, a postdoctoral associate in my laboratory, in collaboration with
Dr. Bruce Hammock (UC Davis), will test the hypothesis that maternal exposure of wild type (WT) mice to the
PAH benzo[a]pyrene (BP) on gestational days 16-19, followed by postnatal hyperoxia (80% oxygen) for 14
days will lead to exacerbation of alveolar simplification of newborn mice on postnatal day (PND) 15 , and that
combined treatment of newborn mice with soluble epoxide hydrolase (sEH) inhibitor (sEHI) 1-
trifluoromethoxyphenyl-3-(1-propionyl-4-yl)urea (TPPU) and oxygen will lead to protection against lung injury,
compared to vehicle-treated mice. He hypothesizes that linoleic acid metabolites such as leukotoxin diols
[dihydroxyoctadecenoic acids (DiHOMEs)] are elevated in mice exposed to hyperoxia, and this phenomenon is
exacerbated in mice pretreated with BP, leading to increased lung injury. We postulate that mice treated with
TPPU will show protection against lung injury. We propose the following Specific Aim: 1. To test the
hypothesis that prenatal exposure of wild type (WT) (C57BL/6J) mice to the PAH BP will result in exacerbation
of lung injury and alveolar simplification following postnatal hyperoxia, and this effect will be attenuated in
newborn mice treated with sEH inhibitor, TPPU. Timed pregnant WT mice will be treated orally with corn oil
(vehicle control) (CO) or BP (15 mg/kg), on gestational days 16-19, and newborns will be delivered at full term
(day 21). These doses are relevant to human exposures, and to women living near Superfund sites. The
newborns will be divided into two groups, with one group receiving TPPU only every other day by i.p for 14
days, and other group will be given the vehicle CO. These mice will be further divided in to 2 groups, one
group to be maintained in room air, and the other exposed to hyperoxia (80% O2) for 14 days, and animals will
be sacrificed on postnatal day (PND) 15 or PND 30. Lung injury and abnormal lung alveolarization will be
assessed. We will also assess cytokine levels, levels of oxylipins, including leukotoxin diols, will measured in
lungs by UPLC/MS-MS on PND15. If successful, leukotoxin diols have the potential of being developed as
novel biomarkers of BPD.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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BHAGAVATULA MOORTHY的其他文献
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{{ truncateString('BHAGAVATULA MOORTHY', 18)}}的其他基金
Mechanisms of exacerbation of COVID-19 pathogenesis in mice expressing human ACE2 by polycyclic aromatic hydrocarbons (PAHs), and its protection by inhibition of soluble epoxide hydrolase (sEH)
多环芳烃 (PAH) 表达人 ACE2 的小鼠中 COVID-19 发病机制恶化,以及通过抑制可溶性环氧化物水解酶 (sEH) 对其进行保护
- 批准号:
10156460 - 财政年份:2021
- 资助金额:
$ 1.61万 - 项目类别:
Mechanisms of exacerbation of COVID-19 pathogenesis in mice expressing human ACE2 by polycyclic aromatic hydrocarbons (PAHs), and its protection by inhibition of soluble epoxide hydrolase (sEH)
多环芳烃 (PAH) 表达人 ACE2 的小鼠中 COVID-19 发病机制恶化,以及通过抑制可溶性环氧化物水解酶 (sEH) 对其进行保护
- 批准号:
10337295 - 财政年份:2021
- 资助金额:
$ 1.61万 - 项目类别:
POLYCYCLIC AROMATIC HYDROCARBONS: ULTRASENSITIVE DETECTION, EARLY LIFE EXPOSURES-CLINICAL OUTCOMES (PRETERM BIRTHS, CHRONIC LUNG DISEASE, AND NEUROCOGNITIVE DEFICITS), PREVENTION AND REMEDIATION
多环芳烃:超灵敏检测、生命早期暴露-临床结果(早产、慢性肺病和神经认知缺陷)、预防和补救
- 批准号:
10401127 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
Proj3:Role of cytochrome P450 (CYP)1A/1B1 enzymes in the potentiation of neonatal lung injury in newbron mice exposed prenatally to PHs, and increased risk of premature infants to chronic lung disease
Proj3:细胞色素 P450 (CYP)1A/1B1 酶在产前暴露于 PH 的新生小鼠中增强新生儿肺损伤中的作用,并增加早产儿患慢性肺病的风险
- 批准号:
10116394 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
Proj3:Role of cytochrome P450 (CYP)1A/1B1 enzymes in the potentiation of neonatal lung injury in newbron mice exposed prenatally to PHs, and increased risk of premature infants to chronic lung disease
Proj3:细胞色素 P450 (CYP)1A/1B1 酶在产前暴露于 PH 的新生小鼠中增强新生儿肺损伤中的作用,并增加早产儿患慢性肺病的风险
- 批准号:
10559705 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
Core A: Administrative and Research Translation Core (ARTC)
核心 A:行政和研究翻译核心 (ARTC)
- 批准号:
10116385 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
POLYCYCLIC AROMATIC HYDROCARBONS: ULTRASENSITIVE DETECTION, EARLY LIFE EXPOSURES-CLINICAL OUTCOMES (PRETERM BIRTHS, CHRONIC LUNG DISEASE, AND NEUROCOGNITIVE DEFICITS), PREVENTION AND REMEDIATION
多环芳烃:超灵敏检测、生命早期暴露-临床结果(早产、慢性肺病和神经认知缺陷)、预防和补救
- 批准号:
10559666 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
Core A: Administrative and Research Translation Core (ARTC)
核心 A:行政和研究翻译核心 (ARTC)
- 批准号:
10559668 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
POLYCYCLIC AROMATIC HYDROCARBONS: ULTRASENSITIVE DETECTION, EARLY LIFE EXPOSURES-CLINICAL OUTCOMES (PRETERM BIRTHS, CHRONIC LUNG DISEASE, AND NEUROCOGNITIVE DEFICITS), PREVENTION AND REMEDIATION
多环芳烃:超灵敏检测、生命早期暴露-临床结果(早产、慢性肺病和神经认知缺陷)、预防和补救
- 批准号:
10116383 - 财政年份:2020
- 资助金额:
$ 1.61万 - 项目类别:
Mechanistic role of P4501 enzymes in the prevention of PAH carcinogenesis by omega 3 fatty acids
P4501 酶在 omega 3 脂肪酸预防 PAH 致癌中的机制作用
- 批准号:
10163846 - 财政年份:2018
- 资助金额:
$ 1.61万 - 项目类别:
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