Abstract 3703: The Effect of Naringenin and Antiarrhythmic Drugs on IKr Inhibition
Grapefruit juice has been reported to cause significant QT prolongation in healthy volunteers. Naringenin (N), the principal flavonoid in grapefruit juice, has been identified as the most potent HERG channel blocker among several dietary flavonoids. We evaluated the effect of combining N with IKr inhibiting antiarrhythmic drugs on the cardiac IKr channel. The effect of N combined with quinidine (Q), dofetilide (D) and amiodarone (A) were studied in an oocyte system with heterogeneously expressed human-ether-a-go-go-related gene (HERG) employing two electrodes voltage clamp technique for recording. The recording solution contained 96mM Na Cl, 5.0mM KCl, 2.0mM CaCl2, and 1.0mM MgCl2, 5mM HEPES and the pH of solution was adjusted with NaOH to 7.4. The experiments were performed at room temperature. N 100uM was found to inhibit HERG current by 31±6% and Q at 1 and 10uM cause 10±1 and 26±3% inhibition of HERG. N 100uM plus 1uM Q caused a 48±5% current inhibition. N 100uM plus 10uM Q caused a 58±6% block in HERG current. N 100uM combined with 1uM D and N 100uM combined with 10uM D caused 56±5 and 90±2% inhibition in HERG current, while D 1 and 10uM alone inhibited current 22±4 and 69±4% respectively. A 1uM decreased current by 20±2% and by 38±8% when combined with 100uM N. A 10uM alone caused 43±4% inhibition and the inhibition increased to 53±9% with the combination of 100uM N. N inhibits IKr and there is an additive inhibitory effect on IKr when N is combined with other IKr blocking antiarrhythmic drugs (Q, D and A). The additive IKr inhibition could pose an increased health risk by increasing repolarization delay and that could give rise to cardiac arrhythmias.