Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional do INMETRO |
Texto Completo: | http://hdl.handle.net/10926/1930 |
Resumo: | Amiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas’ disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC50 values were 4.21 and 0.46 μMagainst promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage.We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (ΔΨm) and to an increase in the production of reactive oxygen species, in a dose-dependent manner. Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes. Other ultrastructural alterations included (1) presence of numerous lipid-storage bodies, (2) presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3) alterations in the chromatin condensation and plasma membrane integrity. Taken together, our results indicate that AMIO is a potent inhibitor of L. amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy. |
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info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAntiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis20112013-01-16T12:27:10Z2013-01-16T12:27:10ZAmiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas’ disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC50 values were 4.21 and 0.46 μMagainst promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage.We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (ΔΨm) and to an increase in the production of reactive oxygen species, in a dose-dependent manner. Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes. Other ultrastructural alterations included (1) presence of numerous lipid-storage bodies, (2) presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3) alterations in the chromatin condensation and plasma membrane integrity. Taken together, our results indicate that AMIO is a potent inhibitor of L. amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy.12 p. : il., tab.Submitted by Lívia Oliveira (livia.oliveira2@hotmail.com) on 2012-08-06T14:39:57Z No. of bitstreams: 1 Souza4_2011.pdf: 2261810 bytes, checksum: 02d19a708127b157bda071b540a120e3 (MD5)Approved for entry into archive by Regina Mello(mrmello@inmetro.gov.br) on 2013-01-16T12:27:10Z (GMT) No. of bitstreams: 1 Souza4_2011.pdf: 2261810 bytes, checksum: 02d19a708127b157bda071b540a120e3 (MD5)Made available in DSpace on 2013-01-16T12:27:10Z (GMT). No. of bitstreams: 1 Souza4_2011.pdf: 2261810 bytes, checksum: 02d19a708127b157bda071b540a120e3 (MD5) Previous issue date: 2011enghttp://hdl.handle.net/10926/1930DMD_hdl_10926/1930SILVA, Sara Teixeira de Macedo et al. Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis. Molecular Biology International, v. 2011, 2011.Silva, Sara Teixeira de MacedoSilva, Thais Larissa Araújo de OliveiraUrbina, Julio A.Souza, Wanderley deRodrigues, Juliany Cola Fernandesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional do INMETROinstname:Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO)instacron:INMETROSilva_2011.pdfhttp://xrepo01s.inmetro.gov.br/bitstream/10926/1930/1/Silva_2011.pdfapplication/pdf2261810http://xrepo01s.inmetro.gov.br/bitstream/10926/1930/1/Silva_2011.pdf02d19a708127b157bda071b540a120e3MD510926_1930_1Silva_2011.pdf.txthttp://xrepo01s.inmetro.gov.br/bitstream/10926/1930/6/Silva_2011.pdf.txttext/plain43868http://xrepo01s.inmetro.gov.br/bitstream/10926/1930/6/Silva_2011.pdf.txt3f8de4aaba386c43dea81b426713b76dMD510926_1930_62024-06-10T15:24:56Zoai:xrepo01s.inmetro.gov.br:10926/1930Repositório de Publicaçõeshttp://repositorios.inmetro.gov.br/oai/requestopendoar:2013-01-17T04:00:09Repositório Institucional do INMETRO - Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO)false |
dc.title.none.fl_str_mv |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
title |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
spellingShingle |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis Silva, Sara Teixeira de Macedo |
title_short |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
title_full |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
title_fullStr |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
title_full_unstemmed |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
title_sort |
Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis |
author |
Silva, Sara Teixeira de Macedo |
author_facet |
Silva, Sara Teixeira de Macedo Silva, Thais Larissa Araújo de Oliveira Urbina, Julio A. Souza, Wanderley de Rodrigues, Juliany Cola Fernandes |
author_role |
author |
author2 |
Silva, Thais Larissa Araújo de Oliveira Urbina, Julio A. Souza, Wanderley de Rodrigues, Juliany Cola Fernandes |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Silva, Sara Teixeira de Macedo Silva, Thais Larissa Araújo de Oliveira Urbina, Julio A. Souza, Wanderley de Rodrigues, Juliany Cola Fernandes |
description |
Amiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas’ disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC50 values were 4.21 and 0.46 μMagainst promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage.We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (ΔΨm) and to an increase in the production of reactive oxygen species, in a dose-dependent manner. Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes. Other ultrastructural alterations included (1) presence of numerous lipid-storage bodies, (2) presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3) alterations in the chromatin condensation and plasma membrane integrity. Taken together, our results indicate that AMIO is a potent inhibitor of L. amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011 |
dc.date.available.fl_str_mv |
2013-01-16T12:27:10Z |
dc.date.accessioned.fl_str_mv |
2013-01-16T12:27:10Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10926/1930 DMD_hdl_10926/1930 |
dc.identifier.citation.fl_str_mv |
SILVA, Sara Teixeira de Macedo et al. Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis. Molecular Biology International, v. 2011, 2011. |
url |
http://hdl.handle.net/10926/1930 |
identifier_str_mv |
DMD_hdl_10926/1930 SILVA, Sara Teixeira de Macedo et al. Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis. Molecular Biology International, v. 2011, 2011. |
dc.language.iso.fl_str_mv |
eng |
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eng |
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application/pdf text/plain |
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