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Effects of Zileuton on Airway Smooth Muscle Remodeling after Repeated Allergen Challenge in Brown Norway Rats.
- Source :
- Respiration; Dec2013, Vol. 86 Issue 5, p421-429, 9p, 1 Chart, 4 Graphs
- Publication Year :
- 2013
-
Abstract
- Background: Chronic asthma is characterized by airway inflammation and remodeling. Objective: This study aimed to evaluate the effects of zileuton on bronchial hyperresponsiveness, airway inflammation and airway smooth muscle (ASM) remodeling. Methods: Two experimental groups of brown Norway rats sensitized and repeatedly challenged with aerosolized ovalbumin (OA) were given oral zileuton (OA-zileuton group) and oral saline only (OA-saline group). A third, control group was sensitized and challenged by saline. The rats were anesthetized and paralyzed. Pulmonary function tests were performed at baseline and after varying doses of acetylcholine. Bronchoalveolar lavage fluid and lung tissues were examined. Results: Zileuton had beneficial effects on pulmonary function, airway inflammation and ASM remodeling in the OA-zileuton group compared to the OA-saline group. Zileuton inhibited an OA-stimulated increase in ASM by inhibiting hypertrophy, hyperplasia and increased extracellular matrix via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, thereby reducing cyclin D1 expression and attenuating bronchial hyperresponsiveness. Conclusion: OA increases airway inflammation and ASM mass. Zileuton effectively prevents bronchial hyperresponsiveness, airway inflammation and ASM remodeling in sensitized rats through the PI3K/Akt pathway, which reduces cyclin D1 expression. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Subjects :
- DRUG therapy for asthma
ALLERGENS
ANALYSIS of variance
ANIMAL experimentation
ASTHMA
CYTOKINES
ENZYME inhibitors
ENZYME-linked immunosorbent assay
IMMUNOHISTOCHEMISTRY
OXIDOREDUCTASES
POLYMERASE chain reaction
RATS
RESEARCH funding
PULMONARY function tests
SMOOTH muscle
STATISTICS
T-test (Statistics)
WESTERN immunoblotting
DATA analysis
REVERSE transcriptase polymerase chain reaction
DATA analysis software
DESCRIPTIVE statistics
CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 00257931
- Volume :
- 86
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Respiration
- Publication Type :
- Academic Journal
- Accession number :
- 93274546
- Full Text :
- https://doi.org/10.1159/000353427