Investigation of cardiac glycosides from oleander in a human induced pluripotent stem cells derived cardiomyocyte model.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Amsterdam, Elsevier/North Holland.
    • Subject Terms:
      Cardenolides/*toxicity ; Cardiac Glycosides/*toxicity ; Cells, Cultured/*drug effects ; Induced Pluripotent Stem Cells/*drug effects ; Myocytes, Cardiac/*drug effects ; Nerium/*toxicity ; Plant Poisoning/*physiopathology; Cardiac Glycosides/chemistry ; Humans ; Nerium/chemistry
    • Abstract:
      The ingestion of Nerium oleander and Thevetia peruviana are common causes for poisoning in Southeast Asia. All parts of the oleander shrub contain cardiac glycosides of the cardenolide type. These glycosides act via inhibition of a Na + /K + -ATPase which might cause severe arrhythmia and subsequent death in oleander-poisoned patients. The current study uses human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) in a microelectrode array (MEA) system to assess the cardiac effects of neriifolin, oleandrin, digitoxigenin, peruvoside and thevetin A from the oleander plant. Digoxin was used as established reference compound. All tested compounds showed a corrected field potential duration (FPDc) shortening and was the lowest for 600 nM digitoxigenin with -36.9 ± 1.2 %. Next to the dose-dependent pro-arrhythmic potential, a complete beat arrest of the spontaneously beating hiPSC-CM was observed at a concentration of 300 nM for neriifolin, 600 nM for oleandrin and 1000 nM for digitoxigenin and peruvoside. Thevetin A did not cause arrhythmia up to a final concentration of 1000 nM. Thus, it was possible to establish a cardiac effect rank order of the tested substances: neriifolin > oleandrin > digitoxigenin = peruvoside > digoxin > thevetin A.
      Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest. The study was funded by the German Ministry of Defence. However, the design, performance, data interpretation and manuscript writing was under the control of the authors and has not been influenced by the German Ministry of Defence.
      (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Arrhythmia; Cardiac glycoside; Cardiotoxicity; Microelectrode array; Oleander poisoning
    • Accession Number:
      0 (Cardenolides)
      0 (Cardiac Glycosides)
    • Publication Date:
      Date Created: 20210809 Date Completed: 20210920 Latest Revision: 20210920
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.toxlet.2021.07.020
    • Accession Number:
      34371141