Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis.
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/4585 https://doi.org/10.1371/journal.pone.0104055 |
Resumo: | Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. Methodology/Principal Findings:: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. Conclusions/Significance:: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment. |
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Castro, Renata Alves de Oliveira eBarcellos, Neila Marcia SilvaLicio, Carolina Souza AndradeSouza, Janine Braga deTestasicca, Miriam Conceição de SouzaFerreira, Flávia MonteiroBatista, Maurício AzevedoLemos, Denise da SilveiraMoura, Sandra Aparecida Lima deFrezard, Frederic Jean GeorgesRezende, Simone Aparecida2015-03-10T17:47:25Z2015-03-10T17:47:25Z2014CASTRO, R. A. O. et al. Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis. Plos One, v. 9, p. e104055, 2014. Disponível em: <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0104055>. Acesso em: 08 nov. 2014.1932-6203http://www.repositorio.ufop.br/handle/123456789/4585https://doi.org/10.1371/journal.pone.0104055Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. Methodology/Principal Findings:: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. Conclusions/Significance:: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.Visceral leishmaniasis - vaccineDisease tropicalAssociation of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleOs trabalhos publicados na Plos one estão sob Licença Creative Commons que permite copiar, distribuir e transmitir o trabalho, desde que sejam citados o autor e licenciante. Não permite o uso para fins comerciais nem a adaptação. Fonte: Plos one <https://www.plos.org/open-access>. Acesso em: 03 jan. 2017.info:eu-repo/semantics/openAccessengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOPLICENSElicense.txtlicense.txttext/plain; charset=utf-82636http://www.repositorio.ufop.br/bitstream/123456789/4585/2/license.txtc2ffdd99e58acf69202dff00d361f23aMD52ORIGINALARTIGO_AssociationLiposomeEncapsulated.pdfARTIGO_AssociationLiposomeEncapsulated.pdfapplication/pdf1501761http://www.repositorio.ufop.br/bitstream/123456789/4585/1/ARTIGO_AssociationLiposomeEncapsulated.pdfbce63c8a2028cb817c98f03b15c23287MD51123456789/45852019-06-24 11:50:09.436oai:localhost: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Repositório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332019-06-24T15:50:09Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.pt_BR.fl_str_mv |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
title |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
spellingShingle |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. Castro, Renata Alves de Oliveira e Visceral leishmaniasis - vaccine Disease tropical |
title_short |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
title_full |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
title_fullStr |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
title_full_unstemmed |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
title_sort |
Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral. leishmaniasis. |
author |
Castro, Renata Alves de Oliveira e |
author_facet |
Castro, Renata Alves de Oliveira e Barcellos, Neila Marcia Silva Licio, Carolina Souza Andrade Souza, Janine Braga de Testasicca, Miriam Conceição de Souza Ferreira, Flávia Monteiro Batista, Maurício Azevedo Lemos, Denise da Silveira Moura, Sandra Aparecida Lima de Frezard, Frederic Jean Georges Rezende, Simone Aparecida |
author_role |
author |
author2 |
Barcellos, Neila Marcia Silva Licio, Carolina Souza Andrade Souza, Janine Braga de Testasicca, Miriam Conceição de Souza Ferreira, Flávia Monteiro Batista, Maurício Azevedo Lemos, Denise da Silveira Moura, Sandra Aparecida Lima de Frezard, Frederic Jean Georges Rezende, Simone Aparecida |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Castro, Renata Alves de Oliveira e Barcellos, Neila Marcia Silva Licio, Carolina Souza Andrade Souza, Janine Braga de Testasicca, Miriam Conceição de Souza Ferreira, Flávia Monteiro Batista, Maurício Azevedo Lemos, Denise da Silveira Moura, Sandra Aparecida Lima de Frezard, Frederic Jean Georges Rezende, Simone Aparecida |
dc.subject.por.fl_str_mv |
Visceral leishmaniasis - vaccine Disease tropical |
topic |
Visceral leishmaniasis - vaccine Disease tropical |
description |
Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. Methodology/Principal Findings:: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. Conclusions/Significance:: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014 |
dc.date.accessioned.fl_str_mv |
2015-03-10T17:47:25Z |
dc.date.available.fl_str_mv |
2015-03-10T17:47:25Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
CASTRO, R. A. O. et al. Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis. Plos One, v. 9, p. e104055, 2014. Disponível em: <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0104055>. Acesso em: 08 nov. 2014. |
dc.identifier.uri.fl_str_mv |
http://www.repositorio.ufop.br/handle/123456789/4585 |
dc.identifier.issn.none.fl_str_mv |
1932-6203 |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1371/journal.pone.0104055 |
identifier_str_mv |
CASTRO, R. A. O. et al. Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis. Plos One, v. 9, p. e104055, 2014. Disponível em: <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0104055>. Acesso em: 08 nov. 2014. 1932-6203 |
url |
http://www.repositorio.ufop.br/handle/123456789/4585 https://doi.org/10.1371/journal.pone.0104055 |
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