Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells
Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, is an important public health problem mainly in Latin America, leading to approximately 12,000 annual deaths. Current etiological treatment for CD is limited to two nitro compounds, benznidazole (Bz...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.975931/full |
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| author | Juliana Magalhães Chaves Barbosa Yasmin Pedra-Rezende Luíza Dantas Pereira Tatiana Galvão de Melo Helene Santos Barbosa Joseli Lannes-Vieira Solange Lisboa de Castro Anissa Daliry Kelly Salomão |
| author_facet | Juliana Magalhães Chaves Barbosa Yasmin Pedra-Rezende Luíza Dantas Pereira Tatiana Galvão de Melo Helene Santos Barbosa Joseli Lannes-Vieira Solange Lisboa de Castro Anissa Daliry Kelly Salomão |
| author_sort | Juliana Magalhães Chaves Barbosa |
| collection | DOAJ |
| description | Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, is an important public health problem mainly in Latin America, leading to approximately 12,000 annual deaths. Current etiological treatment for CD is limited to two nitro compounds, benznidazole (Bz) and nifurtimox (Nif), both presenting relevant limitations. Different approaches have been employed to establish more effective and safer schemes to treat T. cruzi infection, mostly based on drug repurposing and combination therapies. Amiodarone (AMD), an antiarrhythmic medicament of choice for patients with the chronic cardiac form of CD, is also recognized as a trypanocidal agent. Therefore, our aim is to investigate the combined treatment Bz + AMD on trypomastigote viability, control of T. cruzi intracellular form proliferation, and recovery of the infection-induced cytoskeleton alterations in cardiac cells. The combination of Bz + AMD did not improve the direct trypanocidal effect of AMD on the infective blood trypomastigote and replicative intracellular forms of the parasite. Otherwise, the treatment of T. cruzi-infected cardiac cells with Bz plus AMD attenuated the infection-triggered cytoskeleton damage of host cells and the cytotoxic effects of AMD. Thus, the combined treatment Bz + AMD may favor parasite control and hamper tissue damage. |
| first_indexed | 2024-12-11T00:31:13Z |
| format | Article |
| id | doaj.art-39b4615c95fa44f8aec504533d789357 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-11T00:31:13Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-39b4615c95fa44f8aec504533d7893572022-12-22T01:27:20ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-08-011210.3389/fcimb.2022.975931975931Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cellsJuliana Magalhães Chaves Barbosa0Yasmin Pedra-Rezende1Luíza Dantas Pereira2Tatiana Galvão de Melo3Helene Santos Barbosa4Joseli Lannes-Vieira5Solange Lisboa de Castro6Anissa Daliry7Kelly Salomão8Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Ultraestrutura Celular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratóriode de Biologia Estrutural, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Biologia das Interações, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Investigação Cardiovascular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, BrazilChagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, is an important public health problem mainly in Latin America, leading to approximately 12,000 annual deaths. Current etiological treatment for CD is limited to two nitro compounds, benznidazole (Bz) and nifurtimox (Nif), both presenting relevant limitations. Different approaches have been employed to establish more effective and safer schemes to treat T. cruzi infection, mostly based on drug repurposing and combination therapies. Amiodarone (AMD), an antiarrhythmic medicament of choice for patients with the chronic cardiac form of CD, is also recognized as a trypanocidal agent. Therefore, our aim is to investigate the combined treatment Bz + AMD on trypomastigote viability, control of T. cruzi intracellular form proliferation, and recovery of the infection-induced cytoskeleton alterations in cardiac cells. The combination of Bz + AMD did not improve the direct trypanocidal effect of AMD on the infective blood trypomastigote and replicative intracellular forms of the parasite. Otherwise, the treatment of T. cruzi-infected cardiac cells with Bz plus AMD attenuated the infection-triggered cytoskeleton damage of host cells and the cytotoxic effects of AMD. Thus, the combined treatment Bz + AMD may favor parasite control and hamper tissue damage.https://www.frontiersin.org/articles/10.3389/fcimb.2022.975931/fullTrypanosoma cruziChagas diseaseamiodaronebenznidazolecombined treatment |
| spellingShingle | Juliana Magalhães Chaves Barbosa Yasmin Pedra-Rezende Luíza Dantas Pereira Tatiana Galvão de Melo Helene Santos Barbosa Joseli Lannes-Vieira Solange Lisboa de Castro Anissa Daliry Kelly Salomão Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells Frontiers in Cellular and Infection Microbiology Trypanosoma cruzi Chagas disease amiodarone benznidazole combined treatment |
| title | Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells |
| title_full | Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells |
| title_fullStr | Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells |
| title_full_unstemmed | Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells |
| title_short | Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells |
| title_sort | benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in trypanosoma cruzi infected cardiac cells |
| topic | Trypanosoma cruzi Chagas disease amiodarone benznidazole combined treatment |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.975931/full |
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