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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

Title
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
Min Soo Park;Myung Hyun Sohn;Chul Lee;Ran Namgung;Moon Sung Park;Kyu-Earn Kim
Issue Date
2011
Journal Title
Lung
ISSN
0341-2040
Citation
Lung, Vol.189(1) : 43~50, 2011
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.
URI
http://link.springer.com/article/10.1007%2Fs00408-010-9264-1

http://ir.ymlib.yonsei.ac.kr/handle/22282913/93386
DOI
10.1007/s00408-010-9264-1
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pediatrics
Yonsei Authors
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