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Celecoxib Can Adversely Affect Heart Rhythm, Study Suggests

Date:
January 17, 2008
Source:
American Society for Biochemistry and Molecular Biology
Summary:
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.
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The attached image shows the larval heart from Drosophila on which many of the experiments were done. The arrows point to the walls of the heart. The upper frame shows the heart in its dilated form and the lower frame shows the heart after contraction.
Credit: Satpal Singh

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.


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The above post is reprinted from materials provided by American Society for Biochemistry and Molecular Biology. Note: Materials may be edited for content and length.


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American Society for Biochemistry and Molecular Biology. "Celecoxib Can Adversely Affect Heart Rhythm, Study Suggests." ScienceDaily. ScienceDaily, 17 January 2008. <www.sciencedaily.com/releases/2008/01/080114173854.htm>.
American Society for Biochemistry and Molecular Biology. (2008, January 17). Celecoxib Can Adversely Affect Heart Rhythm, Study Suggests. ScienceDaily. Retrieved September 2, 2015 from www.sciencedaily.com/releases/2008/01/080114173854.htm
American Society for Biochemistry and Molecular Biology. "Celecoxib Can Adversely Affect Heart Rhythm, Study Suggests." ScienceDaily. www.sciencedaily.com/releases/2008/01/080114173854.htm (accessed September 2, 2015).

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