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
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Min Soo Park • Myung Hyun Sohn • Kyu-Earn Kim • Moon Sung Park • Ran Namgung • Chul Lee
- چاپ و سال / کشور: 2011
Description
Bronchopulmonary dysplasia is characterized by prolonged oxygen dependency due to compromised gasexchange capability. This is attributable mainly to inadequate and aberrant alveolarization resulting from insults like hyperoxia. Leukotrienes are associated with hyperoxiainduced 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 timedependent 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.
Lung (2011) 189:43–50 DOI 10.1007/s00408-010-9264-1 Received: 28 July 2010 / Accepted: 18 October 2010 / Published online: 5 November 2010
