| Authors | Zitron E, Scholz E, Owen RW, Luck S, Kiesecker C, Thomas D, Kathofer S, Niroomand F, Kiehn J, Kreye VA, Katus HA, Schoels W, Karle CA. | |
| Title | QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids | |
| Full source | Circulation. 2005 Feb 22;111(7):835-8 | |
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 Per scorrere le diapositive |
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| Abstract | BACKGROUND:
A high intake of dietary flavonoids, which are abundant in fruits, vegetables,
tea, and wine, is known to reduce cardiovascular mortality. The effects
of flavonoids on cardiac electrophysiology, which theoretically may have
both antiarrhythmic and proarrhythmic consequences, have not been studied
systematically to date. METHODS AND RESULTS: We screened a broad spectrum
of flavonoids for their inhibitory activity on HERG channels by using heterologous
expression in Xenopus oocytes. At a concentration of 1 mmol/L, 10 compounds
caused a significant inhibition of HERG currents, whereas 11 other flavonoids
had no effect. The IC50 value for HERG block by naringenin, the most potent
inhibitor, was 102.3 micromol/L in Xenopus oocytes and 36.5 micromol/L in
HEK cells. To demonstrate the physiological relevance of these findings,
we studied the effects of pink grapefruit juice, which contains large amounts
of naringenin glycosides (>1000 micromol/L), in human volunteers. In
10 persons, we observed a peak QTc prolongation of 12.5+/-4.2 ms 5 hours
after oral ingestion of 1 L of grapefruit juice. This effect was significant
(P=0.02). CONCLUSIONS: We found a significant QTc prolongation by grapefruit
juice in healthy volunteers, probably caused by block of HERG channels by
flavonoids. These findings reveal new perspectives on the potential for
dietary modification of cardiac electrophysiology. |
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