Document Detail

QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids.
MedLine Citation:
PMID:  15710766     Owner:  NLM     Status:  MEDLINE    
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.
Edgar Zitron; Eberhard Scholz; Robert W Owen; Sonja Lück; Claudia Kiesecker; Dierk Thomas; Sven Kathöfer; Feraydoon Niroomand; Johann Kiehn; Volker A W Kreye; Hugo A Katus; Wolfgang Schoels; Christoph A Karle
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-02-14
Journal Detail:
Title:  Circulation     Volume:  111     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-22     Completed Date:  2005-10-27     Revised Date:  2008-10-28    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  835-8     Citation Subset:  AIM; IM    
Department of Cardiology, University of Heidelberg Medical School, Heidelberg, Germany.
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MeSH Terms
Anti-Arrhythmia Agents
Cation Transport Proteins / antagonists & inhibitors*
Citrus paradisi / chemistry*
Ether-A-Go-Go Potassium Channels
Flavanones / pharmacology
Flavonoids / administration & dosage,  pharmacology*
Inhibitory Concentration 50
Potassium Channels, Voltage-Gated / antagonists & inhibitors*
Transduction, Genetic
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Cation Transport Proteins; 0/ERG1 potassium channel; 0/Ether-A-Go-Go Potassium Channels; 0/Flavanones; 0/Flavonoids; 0/KCNH6 protein, human; 0/Potassium Channels, Voltage-Gated; 480-41-1/naringenin

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