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Cellular electrophysiological effects of the citrus flavonoid hesperetin in dog and rabbit cardiac ventricular preparations.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Flavonoids*/pharmacology ; Hesperidin*/pharmacology; Animals ; Dogs ; Rabbits ; Action Potentials/physiology ; Heart Ventricles ; Potassium/pharmacology
    • Abstract:
      Recent experimental data shows that hesperetin, a citrus flavonoid, affects potassium channels and can prolong the QT c interval in humans. Therefore, in the present study we investigated the effects of hesperetin on various transmembrane ionic currents and on ventricular action potentials. Transmembrane current measurements and action potential recordings were performed by patch-clamp and the conventional microelectrode techniques in dog and rabbit ventricular preparations. At 10 µM concentration hesperetin did not, however, at 30 µM significantly decreased the amplitude of the I K1 , I to , I Kr potassium currents. Hesperetin at 3-30 µM significantly and in a concentration-dependent manner reduced the amplitude of the I Ks current. The drug significantly decreased the amplitudes of the I NaL and I CaL currents at 30 µM. Hesperetin (10 and 30 µM) did not change the action potential duration in normal preparations, however, in preparations where the repolarization reserve had been previously attenuated by 100 nM dofetilide and 1 µg/ml veratrine, caused a moderate but significant prolongation of repolarization. These results suggest that hesperetin at close to relevant concentrations inhibits the I Ks outward potassium current and thereby reduces repolarization reserve. This effect in certain specific situations may prolong the QT interval and consequently may enhance proarrhythmic risk.
      (© 2024. The Author(s).)
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    • Grant Information:
      TKP2021-EGA-32 Ministry of Human Capacities Hungary; EFOP-3.6.2-16-2017-00006 Ministry of Human Capacities Hungary; K 135464 National Research Development and Innovation Office; K 142738 National Research Development and Innovation Office; SZTE AOK-KKA 2022 the Albert Szent-Györgyi Medical School institutional grant; SZTE AOK-KKA 2021 the Albert Szent-Györgyi Medical School institutional grant
    • Contributed Indexing:
      Keywords: Citrus flavonoids; Hesperetin; Proarrhythmia; Repolarization reserve; Transmembrane ionic currents
    • Accession Number:
      0 (Flavonoids)
      Q9Q3D557F1 (hesperetin)
      E750O06Y6O (Hesperidin)
      RWP5GA015D (Potassium)
    • Publication Date:
      Date Created: 20240328 Date Completed: 20240329 Latest Revision: 20240430
    • Publication Date:
      20240430
    • Accession Number:
      PMC10973458
    • Accession Number:
      10.1038/s41598-024-57828-y
    • Accession Number:
      38538818