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Table of Contents
Vol. 110, No. 3, 2008
Issue release date: June 2008
Section title: Original Research
Cardiology 2008;110:145–152
(DOI:10.1159/000111923)

The Additive Effects of the Active Component of Grapefruit Juice (Naringenin) and Antiarrhythmic Drugs on HERG Inhibition

Lin C. · Ke X. · Ranade V. · Somberg J.
Department of Pharmacology, Division of Clinical Pharmacology, Rush University Medical Center, Chicago, Ill., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Research

Received: 4/30/2007
Accepted: 5/10/2007
Published online: 12/4/2007

Number of Print Pages: 8
Number of Figures: 6
Number of Tables: 0

ISSN: 0008-6312 (Print)
eISSN: 1421-9751 (Online)

For additional information: http://www.karger.com/CRD

Abstract

Background: Grapefruit juice causes significant QT prolongation in healthy volunteers and naringenin has been identified as the most potent human ether-a-go-go-related gene (HERG) channel blocker among several dietary flavonoids. The interaction between naringenin and IKr-blocking antiarrhythmic drugs has not been studied. We evaluated the effect of combining naringenin with IKr-inhibiting antiarrhythmic drugs on cardiac IKr. Methods and Results:IKr current was studied by using HERG expressed in Xenopus oocytes, and the two-electrode voltage clamp technique was employed. Antiarrhythmic drugs (azimilide, amiodarone, dofetilide and quinidine) were tested. Experiments were performed at room temperature. Naringenin blocked HERG current dose dependently with an IC50 of 173.3 ± 3.1 µM. Naringenin 100 µM alone inhibited HERG current by 31 ± 6%, and this inhibitory effect was increased with coadministration of 1 or 10 µM antiarrhythmic drugs. When 100 µM naringenin was added to antiarrhythmic drugs, greater HERG inhibition was demonstrated, compared to the current inhibition caused by antiarrhythmic drugs alone. Addition of naringenin significantly increased current inhibition (p < 0.05). Conclusions: There is an additive inhibitory effect on HERG current when naringenin is combined with IKr-blocking antiarrhythmic drugs. This additive HERG inhibition could pose an increased risk of arrhythmias by increasing repolarization delay and possible repolarization heterogeneity.


  

Author Contacts

John Somberg
Division of Clinical Pharmacology
Rush University Medical Center
Chicago, IL 60612 (USA)
Tel. +1 312 942 6590, Fax +1 312 942 5504, E-Mail jsomberg@rush.edu

  

Article Information

Received: April 30, 2007
Accepted after revision: May 10, 2007
Published online: December 4, 2007
Number of Print Pages : 8
Number of Figures : 6, Number of Tables : 0, Number of References : 33

  

Publication Details

Cardiology (International Journal of Cardiovascular Medicine, Surgery, Pathology and Pharmacology)

Vol. 110, No. 3, Year 2008 (Cover Date: June 2008)

Journal Editor: Borer, J.S. (New York, N.Y.)
ISSN: 0008–6312 (Print), eISSN: 1421–9751 (Online)

For additional information: http://www.karger.com/CRD


Article / Publication Details

First-Page Preview
Abstract of Original Research

Received: 4/30/2007
Accepted: 5/10/2007
Published online: 12/4/2007

Number of Print Pages: 8
Number of Figures: 6
Number of Tables: 0

ISSN: 0008-6312 (Print)
eISSN: 1421-9751 (Online)

For additional information: http://www.karger.com/CRD


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