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Celecoxib Shows Non-COX-2 Activity in Heart Cells

Drug affects heart rate and rhythm in experiment on Drosophila flies, which lack COX enzymes

WEDNESDAY, Jan. 23 (HealthDay News) -- Celecoxib may affect the heart independently of cyclooxygenase-2 (COX-2) inhibition, according to research published in the Jan. 18 issue of the Journal of Biological Chemistry.

Roman V. Frolov, of the State University of New York at Buffalo, and colleagues examined celecoxib's effect on the hearts of Drosophila melanogaster -- which both lack cyclooxygenase enzymes and serve as a model for human cardiac pharmacology and cardiomyopathies -- and rat cardiomyocytes.

When exposed to celecoxib, Drosophila heart rate was significantly reduced; after exposure to higher doses, heart rate stopped within seconds. It also induced arrhythmia in the flies. In cultured fetal rat cardiomyocytes, exposure to celecoxib resulted in reduced heart rate and irregular heartbeat. Celecoxib also inhibited delayed rectifier (Kv2) potassium channels in Drosophila, rats, and human embryonic kidney cells. Further evidence of a non-COX action was found when acetylsalicylic acid -- an inhibitor of COX-1 and COX-2 -- failed to inhibit rat Kv2.1 channels.

"The data presented here do not allow for an extrapolation to other selective COX-2 inhibitors because the observed effect did not depend on COX inhibition. Although the previously described cardiovascular complications arising from the prothrombotic effects of coxibs have been seen to a varying degree in the case of most coxibs, the effect described here may or may not translate to other coxibs depending on the nature of the interacting domains between the channel and the drug molecule," the authors write.

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