COX-2 inhibitors like Celecoxib have come under scrutiny lately due to adverse cardiovascular side-effects stemming from COX-2 reduction. In both fruit fly and rat models, researchers reveal another adverse effect of Celecoxib; this drug can induce arrhythmia. More interestingly, this effect is independent of the COX-2 enzyme.
Satpal Singh and colleagues tested various Celecoxib doses on the heart rate of Drosophila, a good model for human cardiac pharmacology. To their surprise, administering 3 ƒÝm Celecoxib (not much higher than the plasma levels in humans taking the drug) reduced heart rate and increased beating irregularities, while 30 ƒÝm was enough to stop the heart within a minute.
The surprise arises from the fact that Drosophila do not have COX-2 enzymes. Rather, Celecoxib could directly inhibit the potassium channels that help generate the electric current that drives heartbeat.
The researchers could achieve similar heart-stopping results in rat cardiac cells, whereas aspirin, another potent COX-2 inhibitor, had no effect, confirming that another mechanism is at work. The drug also inhibited rat and human potassium channels expressed in a human cell line.
Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. They also stress it is too early to speculate on human effects, although their results suggest Drosophila are a valuable tool to investigate other COX-2 drugs.
The above story is based on materials provided by American Society for Biochemistry and Molecular Biology. Note: Materials may be edited for content and length.
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