Abstract |
Bronchopulmonary dysplasia is characterized by prolonged oxygen dependency due to compromised gas-exchange capability. This is attributable mainly to inadequate and aberrant alveolarization resulting from insults like hyperoxia. Leukotrienes are associated with hyperoxia-induced inhibition of alveolarization. We hypothesized that a 5-lipoxygenase-activating protein (FLAP) inhibitor given while newborn mice were exposed to 85% oxygen would prevent aberrant alveolarization in a dose- and time-dependent manner. Newborn mice were exposed to either room air or hyperoxia for 14 days. Pups were treated with either vehicle or MK-0591 10, 20, or 40 mg/kg subcutaneously daily for days 1-4, 5-9, or 10-14. On day 14, the lungs were inflated, fixed, and stained for histopathological and morphometric analyses. Hyperoxia groups treated with MK-0591 20 or 40 mg/kg during days P1-P4 or P10-P14 showed alveolarization that resembled that of room air controls while untreated hyperoxia groups showed definite evidence of aberrant alveolarization but no inflammation. In a hyperoxia-exposed newborn mice model, a FLAP inhibitor given during critical window periods may prevent aberration of alveolarization in a dose- and time-dependent manner.
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Authors | Min Soo Park, Myung Hyun Sohn, Kyu-Earn Kim, Moon Sung Park, Ran Namgung, Chul Lee |
Journal | Lung
(Lung)
Vol. 189
Issue 1
Pg. 43-50
(Feb 2011)
ISSN: 1432-1750 [Electronic] United States |
PMID | 21052705
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 5-Lipoxygenase-Activating Protein Inhibitors
- 5-Lipoxygenase-Activating Proteins
- Alox5ap protein, mouse
- Indoles
- Quinolines
- MK 0591
- Oxygen
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Topics |
- 5-Lipoxygenase-Activating Protein Inhibitors
(administration & dosage, pharmacology)
- 5-Lipoxygenase-Activating Proteins
(metabolism)
- Animals
- Animals, Newborn
- Body Weight
- Bronchopulmonary Dysplasia
(enzymology, etiology, pathology, physiopathology, prevention & control)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Humans
- Hyperoxia
(chemically induced, drug therapy, enzymology, pathology, physiopathology)
- Indoles
(administration & dosage, pharmacology)
- Infant, Newborn
- Injections, Subcutaneous
- Mice
- Oxygen
- Pulmonary Alveoli
(drug effects, enzymology, growth & development, pathology)
- Quinolines
(administration & dosage, pharmacology)
- Time Factors
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