Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/39922
Title: A Combination of Itraconazole and Amiodarone Is Highly Effective against Trypanosoma cruzi Infection of Human Stem Cell-Derived Cardiomyocytes.
Authors: Sass, Gabriele
Madigan, Roy T
Joubert, Lydia Marie
Bozzi, Adriana
Sayed, Nazish
Wu, Joseph C
Stevens, David A
Affilliation: California Institute for Medical Research, San Jose, California.
Animal Hospital of Smithson Valley, Spring Branch, Texas.
EM Unit, Central Analytical Facilities, Stellenbosch University, Stellenbosch, South Africa/Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa.
California Institute for Medical Research, San Jose, California/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil./Division of Cardiology, Department of Medicine, School of Medicine, Stanford University, Stanford, California/School of Medicine, Cardiovascular Institute, Stanford University, Stanford, California.
Division of Cardiology, Department of Medicine, School of Medicine, Stanford University, Stanford, California/ School of Medicine, Cardiovascular Institute, Stanford University, Stanford, California
Division of Cardiology, Department of Medicine, School of Medicine, Stanford University, Stanford, California/ School of Medicine, Cardiovascular Institute, Stanford University, Stanford, California.
California Institute for Medical Research, San Jose, California/Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California
Abstract: Trypanosoma cruzi is the etiologic agent of Chagas disease (CD), which can result in severe cardiomyopathy. Trypanosoma cruzi is endemic to the Americas, and of particular importance in Latin America. In the United States and other non-endemic countries, rising case numbers have also been observed. The currently used drugs are benznidazole (BNZ) and nifurtimox, which have limited efficacy during chronic infection. We repurposed itraconazole (ICZ), originally an antifungal, in combination with amiodarone (AMD), an antiarrhythmic, with the goal of interfering with T. cruzi infection. Human pluripotent stem cells (hiPSCs) were differentiated into cardiomyocytes (hiPSC-CMs). Vero cells or hiPSC-CMs were infected with T. cruzi trypomastigotes of the II or I strain in the presence of ICZ and/or AMD. After 48 hours, cells were Giemsa stained, and infection and multiplication were evaluated microscopically. Trypanosoma cruzi infection and multiplication were evalutated also by electron microscopy. BNZ was used as a reference compound. Cell metabolism in the presence of test substances was assessed. Itraconazole and AMD showed strain- and dose-dependent interference with T. cruzi infection and multiplication in Vero cells or hiPSC-CMs. Combinations of ICZ and AMD were more effective against T. cruzi than the single substances, or BNZ, without affecting host cell metabolism, and better preserving host cell integrity during infection. Our in vitro data in hiPSC-CMs suggest that a combination of ICZ and AMD might serve as a treatment option for CD in patients, but that different responses due to T. cruzi strain differences have to be taken into account.
Issue Date: 2019
Publisher: American Society of Tropical Medicine and Hygiene
Citation: SASS, Gabriele et al. A Combination of Itraconazole and Amiodarone Is Highly Effective against Trypanosoma cruzi Infection of Human Stem Cell-Derived Cardiomyocytes. Am J Trop Med Hyg., v. 101. n. 2, p. 383-391, 2019.
DOI: 10.4269/ajtmh.19-0023
ISSN: 0002-9637
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
A Combination of Itraconazole and Amiodarone Is Highly Effective against .pdf83.47 kBAdobe PDF    Request a copy



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.