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5-Lipoxygenase-activating protein (FLAP) inhibitor MK-0591 prevents aberrant alveolarization in newborn mice exposed to 85% oxygen in a dose- and time-dependent manner.

Authors
Park, MS; Sohn, MH; Kim, KE; Namgung, R; Lee, C
Citation
Lung, 189(1):43-50, 2011
Journal Title
Lung
ISSN
0341-20401432-1750
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.
MeSH terms
5-Lipoxygenase-Activating Protein Inhibitors/administration & dosage/*pharmacology5-Lipoxygenase-Activating Proteins/*metabolismAnimalsAnimals, NewbornBody WeightBronchopulmonary Dysplasia/enzymology/etiology/pathology/physiopathology/*prevention & controlDisease Models, AnimalDose-Response Relationship, DrugHumansHyperoxia/chemically induced/*drug therapy/enzymology/pathology/physiopathologyIndoles/administration & dosage/*pharmacologyInfant, NewbornInjections, SubcutaneousMiceOxygenPulmonary Alveoli/*drug effects/enzymology/growth & development/pathologyQuinolines/administration & dosage/*pharmacologyTime Factors
DOI
10.1007/s00408-010-9264-1
PMID
21052705
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pediatrics & Adolescent Medicine
AJOU Authors
박, 문성
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