Celecoxib Can Adversely Affect Heart Rhythm

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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 μm Celecoxib (not much higher than the plasma levels in humans taking the drug) reduced heart rate and increased beating irregularities, while 30 μm 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 American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society’s student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society’s purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

Source: American Society for Biochemistry and Molecular Biology (ASBMB)

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