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.

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.

• Authors: Min Soo Park, Myung Hyun Sohn, Kyu-Earn Kim, Moon Sung Park, Ran Namgung, Chul Lee
• Journal: Lung (Lung) Vol. 189 Issue 1 Pg. 43-50 (Feb 2011) ISSN: 1432-1750 [Electronic] United States
• PMID: 21052705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-Lipoxygenase-Activating Protein Inhibitors
• 5-Lipoxygenase-Activating Proteins
• Alox5ap protein, mouse
• Indoles
• Quinolines
• MK 0591
• Oxygen

Topics

• 5-Lipoxygenase-Activating Protein Inhibitors (administration & dosage, pharmacology)
• 5-Lipoxygenase-Activating Proteins (metabolism)
• Animals
• Animals, Newborn
• Body Weight
• Bronchopulmonary Dysplasia (enzymology, etiology, pathology, physiopathology, prevention & control)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Humans
• Hyperoxia (chemically induced, drug therapy, enzymology, pathology, physiopathology)
• Indoles (administration & dosage, pharmacology)
• Infant, Newborn
• Injections, Subcutaneous
• Mice
• Oxygen
• Pulmonary Alveoli (drug effects, enzymology, growth & development, pathology)
• Quinolines (administration & dosage, pharmacology)
• Time Factors