Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

CITRUS ALKALOIDS MAY ENHANCE PROARRHYTHMIC RISK

A. Varro 1,2

1 Department of Pharmacology and Pharmacotherapy, University of Szeged, Hungary; 2 MTA SZTE Research Group for Cardiovascular Pharmacology, Eotvos Lorand Research Network, Szeged, Hungary Citrus fruits like lemon, orange or grapefruit are part of the Mediterranean diet and are generally considered beneficial, and as such can increase life expectancy. Important constituent of citrus fruits are the flavonoids. Many studies indicated that flavonoids have anti-ischaemic or anticancer effects. It was however, also reported that consumption of grapefruit and orange juice increase the time of cardiac repolarization manifested as lengthening of the QTc interval in the surface ECG recordings. In addition, grapefruit consumption inhibits important enzyme playing role in the metabolism of several drugs including those which themselves prolong QTc (terfenadine) and were reported that occasionally elicited severe arrhythmias sometimes resulting sudden cardiac death, The exact reason of the effect of the citrus fruits on cardiac repolarization and possible proarrhythmic complication are not well explored and still matter of debate. Some limited number of studies reported that naringenin and hesperidin two alkaloids present relatively high concentration in orange and grapefruit inhibited HERG potassium current in mammalian cell lines, but solid evidence is still missing how these alkaloids affect native cardiac ion channels and action potentials. In this presentation the author makes an attempt to briefly overlook the most important data can be find in the literature in this topic and show some preliminary unpublished data regarding the cellular cardiac electrophysiologic effect of hesperidin on ventricular action potential in dog right ventricular preparation obtained by the conventional microelectrode technique. In addition, by applying the whole cell configuration of the patch-clamp technique effects of hesperidin will be also presented in ventricular myocytes on the rapid and slow delayed rectifier outward potassium currents.

Keywords: proarrhytmia, repolarization reserve, citrus flavonoids, naringenin, hesperidin

Funding:National Research Development and Innovation Office (NKFIH K-135464 and GINOP 2.3.2.-15-2016-00006); the Ministry of Innovation and Technology of Hungary (financed under the TKP2021-EGA funding scheme).

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