• Patchliner

    兼顾科研与工业的全自动膜片钳系统
  • Patchliner

    自主生产与质量控制的耗材
  • Patchliner

    拥有超过10年实验设计与支持的经验
  • Dynamite8

    Automated Dynamic Clamp
  • Patchliner

    拥有所有手动膜片钳的特征与优点

2022 - Synergistic Adverse Effects of Azithromycin and Hydroxychloroquine on Human Cardiomyocytes at a Clinically Relevant Treatment Duration

icon pl  Patchliner Publication in Pharmaceuticals (2022)

Authors:
Li W., Luo X., Poetsch M. S., Oertel R., Nichani K., Schneider M., Strano A., Hasse M., Steiner R-P., Cyganek L., Hettwer K., Uhlig S., Simon K., Guan K., Schubert M.

Journal:
Pharmaceuticals (2022) doi:10.3390/ph15020220


Abstract: 

Adverse effects of drug combinations and their underlying mechanisms are highly relevant for safety evaluation, but often not fully studied. Hydroxychloroquine (HCQ) and azithromycin (AZM) were used as a combination therapy in the treatment of COVID-19 patients at the beginning of the pandemic, leading to higher complication rates in comparison to respective monotherapies. Here, we used human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to systematically investigate the effects of HCQ, AZM, and their combination on the structure and functionality of cardiomyocytes, and to better understand the underlying mechanisms. Our results demonstrate synergistic adverse effects of AZM and HCQ on electrophysiological and contractile function of iPSC-CMs. HCQ-induced prolongation of field potential duration (FPDc) was gradually increased during 7-day treatment period and was strongly enhanced by combination with AZM, although AZM alone slightly shortened FPDc in iPSC-CMs. Combined treatment with AZM and HCQ leads to higher cardiotoxicity, more severe structural disarrangement, more pronounced contractile dysfunctions, and more elevated conduction velocity, compared to respective monotreatments. Mechanistic insights underlying the synergistic effects of AZM and HCQ on iPSC-CM functionality are provided based on increased cellular accumulation of HCQ and AZM as well as increased Cx43- and Nav1.5-protein levels.


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