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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

 Min Soo Park  ;  Myung Hyun Sohn  ;  Kyu-Earn Kim  ;  Moon Sung Park  ;  Ran Namgung  ;  Chul Lee 
 LUNG, Vol.189(1) : 43-50, 2011 
Journal Title
Issue Date
5-Lipoxygenase-Activating Protein Inhibitors/administration & dosage ; 5-Lipoxygenase-Activating Protein Inhibitors/pharmacology* ; 5-Lipoxygenase-Activating Proteins/metabolism* ; Animals ; Animals, Newborn ; Body Weight ; Bronchopulmonary Dysplasia/enzymology ; Bronchopulmonary Dysplasia/etiology ; Bronchopulmonary Dysplasia/pathology ; Bronchopulmonary Dysplasia/physiopathology ; Bronchopulmonary Dysplasia/prevention & control* ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Humans ; Hyperoxia/chemically induced ; Hyperoxia/drug therapy* ; Hyperoxia/enzymology ; Hyperoxia/pathology ; Hyperoxia/physiopathology ; Indoles/administration & dosage ; Indoles/pharmacology* ; Infant, Newborn ; Injections, Subcutaneous ; Mice ; Oxygen ; Pulmonary Alveoli/drug effects* ; Pulmonary Alveoli/enzymology ; Pulmonary Alveoli/growth & development ; Pulmonary Alveoli/pathology ; Quinolines/administration & dosage ; Quinolines/pharmacology* ; Time Factors
Bronchopulmonary dysplasia ; Hyperoxia ; Alveolarization ; Leukotriene ; 5-Lipoxygenase activating protein
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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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyu Earn(김규언)
Namgung, Ran(남궁란) ORCID logo https://orcid.org/0000-0001-7182-9535
Park, Moon Sung(박문성)
Park, Min Soo(박민수) ORCID logo https://orcid.org/0000-0002-4395-9938
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Lee, Chul(이철)
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