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Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi

Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC)...

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Autores principales: de Freitas Oliveira, Johny Wysllas, Torres, Taffarel Melo, Moreno, Cláudia Jassica Gonçalves, Amorim-Carmo, Bruno, Damasceno, Igor Zumba, Soares, Ana Katarina Menezes Cruz, da Silva Barbosa, Jefferson, Rocha, Hugo Alexandre Oliveira, Silva, Marcelo Sousa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159965/
https://www.ncbi.nlm.nih.gov/pubmed/34045624
http://dx.doi.org/10.1038/s41598-021-90719-0
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author de Freitas Oliveira, Johny Wysllas
Torres, Taffarel Melo
Moreno, Cláudia Jassica Gonçalves
Amorim-Carmo, Bruno
Damasceno, Igor Zumba
Soares, Ana Katarina Menezes Cruz
da Silva Barbosa, Jefferson
Rocha, Hugo Alexandre Oliveira
Silva, Marcelo Sousa
author_facet de Freitas Oliveira, Johny Wysllas
Torres, Taffarel Melo
Moreno, Cláudia Jassica Gonçalves
Amorim-Carmo, Bruno
Damasceno, Igor Zumba
Soares, Ana Katarina Menezes Cruz
da Silva Barbosa, Jefferson
Rocha, Hugo Alexandre Oliveira
Silva, Marcelo Sousa
author_sort de Freitas Oliveira, Johny Wysllas
collection PubMed
description Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC(50) of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.
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spelling pubmed-81599652021-05-28 Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi de Freitas Oliveira, Johny Wysllas Torres, Taffarel Melo Moreno, Cláudia Jassica Gonçalves Amorim-Carmo, Bruno Damasceno, Igor Zumba Soares, Ana Katarina Menezes Cruz da Silva Barbosa, Jefferson Rocha, Hugo Alexandre Oliveira Silva, Marcelo Sousa Sci Rep Article Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC(50) of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease. Nature Publishing Group UK 2021-05-27 /pmc/articles/PMC8159965/ /pubmed/34045624 http://dx.doi.org/10.1038/s41598-021-90719-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
de Freitas Oliveira, Johny Wysllas
Torres, Taffarel Melo
Moreno, Cláudia Jassica Gonçalves
Amorim-Carmo, Bruno
Damasceno, Igor Zumba
Soares, Ana Katarina Menezes Cruz
da Silva Barbosa, Jefferson
Rocha, Hugo Alexandre Oliveira
Silva, Marcelo Sousa
Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
title Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
title_full Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
title_fullStr Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
title_full_unstemmed Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
title_short Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
title_sort insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of trypanosoma cruzi
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159965/
https://www.ncbi.nlm.nih.gov/pubmed/34045624
http://dx.doi.org/10.1038/s41598-021-90719-0
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