In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection.
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/10927 |
Resumo: | New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome® , Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis. |
id |
UFOP_d16b96792d082765e529b988b1b95ce9 |
---|---|
oai_identifier_str |
oai:localhost:123456789/10927 |
network_acronym_str |
UFOP |
network_name_str |
Repositório Institucional da UFOP |
repository_id_str |
3233 |
spelling |
Mendonça, Débora Vasconcelos CostaTavares, Grasiele de Sousa VieiraLage, Daniela PagliaraSoyer, Tauane GonçalvesCarvalho, Lívia MendesDias, Daniel SilvaRibeiro, Patrícia Aparecida FernandesOttoni, Flaviano MeloAntinarelli, Luciana Maria RibeiroVale, Danniele LucianaRibeiro, Fernanda LudolfDuarte, Mariana CostaCoimbra, Elaine SoaresChávez Fumagalli, Miguel AngelRoatt, Bruno MendesSouza, Daniel MenezesBarichello, José MarioAlves, Ricardo JoséCoelho, Eduardo Antônio Ferraz2019-04-03T17:31:46Z2019-04-03T17:31:46Z2019MENDONÇA, D. V. C. et al. In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. Biomedicine & Pharmacotherapy, v. 109, p. 779-787, jan. 2019. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0753332218367878>. Acesso em: 22 fev. 2019.07533322http://www.repositorio.ufop.br/handle/123456789/10927New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome® , Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). Fonte: o próprio artigo.info:eu-repo/semantics/openAccessChemotherapyAmphotericin BTegumentary leishmaniasisToxicityIn vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOPLICENSElicense.txtlicense.txttext/plain; charset=utf-8924http://www.repositorio.ufop.br/bitstream/123456789/10927/2/license.txt62604f8d955274beb56c80ce1ee5dcaeMD52ORIGINALARTIGO_VivoAntileishmanialEfficacy.pdfARTIGO_VivoAntileishmanialEfficacy.pdfapplication/pdf1495218http://www.repositorio.ufop.br/bitstream/123456789/10927/1/ARTIGO_VivoAntileishmanialEfficacy.pdf9b422c6d549e01cdf1b19f29bf0c2feaMD51123456789/109272019-04-03 13:31:47.02oai:localhost: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ório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332019-04-03T17:31:47Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.pt_BR.fl_str_mv |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
title |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
spellingShingle |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. Mendonça, Débora Vasconcelos Costa Chemotherapy Amphotericin B Tegumentary leishmaniasis Toxicity |
title_short |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
title_full |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
title_fullStr |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
title_full_unstemmed |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
title_sort |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. |
author |
Mendonça, Débora Vasconcelos Costa |
author_facet |
Mendonça, Débora Vasconcelos Costa Tavares, Grasiele de Sousa Vieira Lage, Daniela Pagliara Soyer, Tauane Gonçalves Carvalho, Lívia Mendes Dias, Daniel Silva Ribeiro, Patrícia Aparecida Fernandes Ottoni, Flaviano Melo Antinarelli, Luciana Maria Ribeiro Vale, Danniele Luciana Ribeiro, Fernanda Ludolf Duarte, Mariana Costa Coimbra, Elaine Soares Chávez Fumagalli, Miguel Angel Roatt, Bruno Mendes Souza, Daniel Menezes Barichello, José Mario Alves, Ricardo José Coelho, Eduardo Antônio Ferraz |
author_role |
author |
author2 |
Tavares, Grasiele de Sousa Vieira Lage, Daniela Pagliara Soyer, Tauane Gonçalves Carvalho, Lívia Mendes Dias, Daniel Silva Ribeiro, Patrícia Aparecida Fernandes Ottoni, Flaviano Melo Antinarelli, Luciana Maria Ribeiro Vale, Danniele Luciana Ribeiro, Fernanda Ludolf Duarte, Mariana Costa Coimbra, Elaine Soares Chávez Fumagalli, Miguel Angel Roatt, Bruno Mendes Souza, Daniel Menezes Barichello, José Mario Alves, Ricardo José Coelho, Eduardo Antônio Ferraz |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Mendonça, Débora Vasconcelos Costa Tavares, Grasiele de Sousa Vieira Lage, Daniela Pagliara Soyer, Tauane Gonçalves Carvalho, Lívia Mendes Dias, Daniel Silva Ribeiro, Patrícia Aparecida Fernandes Ottoni, Flaviano Melo Antinarelli, Luciana Maria Ribeiro Vale, Danniele Luciana Ribeiro, Fernanda Ludolf Duarte, Mariana Costa Coimbra, Elaine Soares Chávez Fumagalli, Miguel Angel Roatt, Bruno Mendes Souza, Daniel Menezes Barichello, José Mario Alves, Ricardo José Coelho, Eduardo Antônio Ferraz |
dc.subject.por.fl_str_mv |
Chemotherapy Amphotericin B Tegumentary leishmaniasis Toxicity |
topic |
Chemotherapy Amphotericin B Tegumentary leishmaniasis Toxicity |
description |
New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome® , Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-04-03T17:31:46Z |
dc.date.available.fl_str_mv |
2019-04-03T17:31:46Z |
dc.date.issued.fl_str_mv |
2019 |
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.citation.fl_str_mv |
MENDONÇA, D. V. C. et al. In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. Biomedicine & Pharmacotherapy, v. 109, p. 779-787, jan. 2019. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0753332218367878>. Acesso em: 22 fev. 2019. |
dc.identifier.uri.fl_str_mv |
http://www.repositorio.ufop.br/handle/123456789/10927 |
dc.identifier.issn.none.fl_str_mv |
07533322 |
identifier_str_mv |
MENDONÇA, D. V. C. et al. In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. Biomedicine & Pharmacotherapy, v. 109, p. 779-787, jan. 2019. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0753332218367878>. Acesso em: 22 fev. 2019. 07533322 |
url |
http://www.repositorio.ufop.br/handle/123456789/10927 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFOP instname:Universidade Federal de Ouro Preto (UFOP) instacron:UFOP |
instname_str |
Universidade Federal de Ouro Preto (UFOP) |
instacron_str |
UFOP |
institution |
UFOP |
reponame_str |
Repositório Institucional da UFOP |
collection |
Repositório Institucional da UFOP |
bitstream.url.fl_str_mv |
http://www.repositorio.ufop.br/bitstream/123456789/10927/2/license.txt http://www.repositorio.ufop.br/bitstream/123456789/10927/1/ARTIGO_VivoAntileishmanialEfficacy.pdf |
bitstream.checksum.fl_str_mv |
62604f8d955274beb56c80ce1ee5dcae 9b422c6d549e01cdf1b19f29bf0c2fea |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP) |
repository.mail.fl_str_mv |
repositorio@ufop.edu.br |
_version_ |
1801685759468503040 |