Journal article
Iloprost attenuates hyperoxia-mediated impairment of lung development in newborn mice
American journal of physiology. Lung cellular and molecular physiology, v 315(4), pp L535-L544
01 Oct 2018
PMID: 29952221
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cyclooxygenase-2 (COX-2/PTGS2) mediates hyperoxia-induced impairment of lung development in newborn animals and is increased in the lungs of human infants with bronchopulmonary dysplasia (BPD). COX-2 catalyzes the production of cytoprotective prostaglandins, such as prostacyclin (PGI
2
), as well as proinflammatory mediators, such as thromboxane A2. Our objective was to determine whether iloprost, a synthetic analog of PGI
2
, would attenuate hyperoxia effects in the newborn mouse lung. To test this hypothesis, newborn C57BL/6 mice along with their dams were exposed to normoxia (21% O
2
) or hyperoxia (85% O
2
) from 4 to 14 days of age in combination with daily intraperitoneal injections of either iloprost 200 µg·kg
−1
·day
−1
, nimesulide (selective COX-2 antagonist) 100 mg·kg
−1
·day
−1
, or vehicle. Alveolar development was estimated by radial alveolar counts and mean linear intercepts. Lung function was determined on a flexiVent, and multiple cytokines and myeloperoxidase (MPO) were quantitated in lung homogenates. Lung vascular and microvascular morphometry was performed, and right ventricle/left ventricle ratios were determined. We determined that iloprost (but not nimesulide) administration attenuated hyperoxia-induced inhibition of alveolar development and microvascular density in newborn mice. Iloprost and nimesulide both attenuated hyperoxia-induced, increased lung resistance but did not improve lung compliance that was reduced by hyperoxia. Iloprost and nimesulide reduced hyperoxia-induced increases in MPO and some cytokines (IL-1β and TNF-α) but not others (IL-6 and KC/Gro). There were no changes in pulmonary arterial wall thickness or right ventricle/left ventricle ratios. We conclude that iloprost improves lung development and reduces lung inflammation in a newborn mouse model of BPD.
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Details
- Title
- Iloprost attenuates hyperoxia-mediated impairment of lung development in newborn mice
- Creators
- Nelida Olave - University of Alabama at BirminghamCharitharth Vivek Lal - University of Alabama at BirminghamBrian Halloran - University of Alabama at BirminghamVineet Bhandari - Drexel UniversityNamasivayam Ambalavanan - University of Alabama at Birmingham
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, v 315(4), pp L535-L544
- Publisher
- American Physiological Society (APS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000447161500007
- Scopus ID
- 2-s2.0-85054413944
- Other Identifier
- 991019167574904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Physiology
- Respiratory System