Comparison of the effects of selected cyclooxygenase enzyme inhibitors on airway responsiveness to histamine and acetyl choline in an experimental model of allergic asthma in guinea pig


1 Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran- Iran

2 Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran- Iran

3 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran- Iran

4 Graduated from Faculty of Veterinary Medicine, University of Tehran, Tehran- Iran


BACKGROUND: Aspirin-induced asthma (AIA) with symptoms such as acute bronchoconstriction occurs in about 10% of asthmatic individuals following ingestion of aspirin or other aspirin-like drugs. The mechanisms involved in AIA are not fully understood but it seems that inhibition of cyclooxygenase (COX) can play a role in such attacks.               Objectives: This study aimed to compare the effects of aspirin-like drugs on airway responsiveness in an animal model of allergic asthma. Methods: 42 male guinea pigs (250-300 g) were randomly divided into seven groups: control, allergic, ketoprofen, indomethacin, celecoxib, and aspirin (high and low doses). All animals except control group were sensitized by i.p. injections of ovalbumin and Al (OH)3 suspensions and then challenged by inhalation of ovalbumin solution on day 18. The animals received three oral doses of the aforementioned drugs or normal saline in control and allergic groups with 12 hr intervals within 24 hr before ovalbumin challenge. On day 19, animals were euthanized and the responsiveness of isolated tracheas was studied using cumulative doses of histamine and acetyl choline in an organ bath. Results: Indomethacin and ketoprofen significantly increased the trachea responsiveness to acetyl choline and histamine at all concentrations. Emax values for acetyl choline and histamine in indomethacin were respectively (3.5±0.1, 3.5±0.1 g) and ketoprofen (5.1±0.2, 4.3±0.1) groups were greater than those of control (1.5±0.1, 1.5±0.1), allergic, celecoxib, high dose aspirin and low dose aspirin groups (p<0.05). Conclusions: It was concluded that indomethacin and ketoprofen (but not aspirin and celecoxib) can exacerbate the asthmatic conditions in this animal model.


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