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.
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.
Department of Pediatrics, Yonsei University College of Medicine, 250 Seongsanno (134 Sinchon-dong) Seodaemun-gu, Seoul 120-752, Korea. minspark@yuhs.ac
Min Soo
MS
Park
Myung Hyun
MH
Sohn
Kyu-Earn
KE
Kim
Moon Sung
MS
Park
Ran
R
Namgung
Chul
C
Lee
D058946:5-Lipoxygenase-Activating Protein Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D058927:5-Lipoxygenase-Activating Proteins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018496:Hyperoxia / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007231:Infant, Newborn; D007279:Injections, Subcutaneous; D051379:Mice; D010100:Oxygen; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D058946:5-Lipoxygenase-Activating Protein Inhibitors; D058927:5-Lipoxygenase-Activating Proteins; C548593:Alox5ap protein, mouse; D007211:Indoles; D011804:Quinolines; C078266:MK 0591; D010100:Oxygen