Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system.
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/8608 https://doi.org/10.1016/j.parint.2016.07.005 |
Resumo: | Newtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered, as well as the evaluation of new molecules that have already shown to present biological activity. In this context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline (8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load. The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines, as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1 isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion, 8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined with other drugs, as an alternative treatment for VL. |
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Duarte, Mariana CostaLage, Letícia Martins dos ReisLage, Daniela PagliaraMartins, Vivian TamiettiCarvalho, Ana Maria Ravena SeverinoRoatt, Bruno MendesSouza, Daniel MenezesTavares, Carlos Alberto PereiraAlves, Ricardo JoséBarichello, José MarioCoelho, Eduardo Antônio Ferraz2017-08-30T18:19:48Z2017-08-30T18:19:48Z2016DUARTE, M. C. et al. Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. Parasitology International, v. 65, p. 728-736, 2016. Disponível em: <http://www.sciencedirect.com/science/article/pii/S1383576916302240?via%3Dihub>. Acesso em: 29 ago. 2017.1383-5769http://www.repositorio.ufop.br/handle/123456789/8608https://doi.org/10.1016/j.parint.2016.07.005Newtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered, as well as the evaluation of new molecules that have already shown to present biological activity. In this context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline (8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load. The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines, as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1 isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion, 8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined with other drugs, as an alternative treatment for VL.ToxicityTreatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOPLICENSElicense.txtlicense.txttext/plain; charset=utf-8924http://www.repositorio.ufop.br/bitstream/123456789/8608/2/license.txt62604f8d955274beb56c80ce1ee5dcaeMD52ORIGINALARTIGO_TreatmentMurineVisceral.pdfARTIGO_TreatmentMurineVisceral.pdfapplication/pdf854290http://www.repositorio.ufop.br/bitstream/123456789/8608/1/ARTIGO_TreatmentMurineVisceral.pdf6d2397813ab21c386b190b34f86080b2MD51123456789/86082020-01-23 06:17:31.29oai:localhost: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ório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332020-01-23T11:17:31Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.pt_BR.fl_str_mv |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
title |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
spellingShingle |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. Duarte, Mariana Costa Toxicity |
title_short |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
title_full |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
title_fullStr |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
title_full_unstemmed |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
title_sort |
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. |
author |
Duarte, Mariana Costa |
author_facet |
Duarte, Mariana Costa Lage, Letícia Martins dos Reis Lage, Daniela Pagliara Martins, Vivian Tamietti Carvalho, Ana Maria Ravena Severino Roatt, Bruno Mendes Souza, Daniel Menezes Tavares, Carlos Alberto Pereira Alves, Ricardo José Barichello, José Mario Coelho, Eduardo Antônio Ferraz |
author_role |
author |
author2 |
Lage, Letícia Martins dos Reis Lage, Daniela Pagliara Martins, Vivian Tamietti Carvalho, Ana Maria Ravena Severino Roatt, Bruno Mendes Souza, Daniel Menezes Tavares, Carlos Alberto Pereira Alves, Ricardo José Barichello, José Mario Coelho, Eduardo Antônio Ferraz |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Duarte, Mariana Costa Lage, Letícia Martins dos Reis Lage, Daniela Pagliara Martins, Vivian Tamietti Carvalho, Ana Maria Ravena Severino Roatt, Bruno Mendes Souza, Daniel Menezes Tavares, Carlos Alberto Pereira Alves, Ricardo José Barichello, José Mario Coelho, Eduardo Antônio Ferraz |
dc.subject.por.fl_str_mv |
Toxicity |
topic |
Toxicity |
description |
Newtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered, as well as the evaluation of new molecules that have already shown to present biological activity. In this context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline (8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load. The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines, as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1 isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion, 8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined with other drugs, as an alternative treatment for VL. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2017-08-30T18:19:48Z |
dc.date.available.fl_str_mv |
2017-08-30T18:19:48Z |
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 |
DUARTE, M. C. et al. Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. Parasitology International, v. 65, p. 728-736, 2016. Disponível em: <http://www.sciencedirect.com/science/article/pii/S1383576916302240?via%3Dihub>. Acesso em: 29 ago. 2017. |
dc.identifier.uri.fl_str_mv |
http://www.repositorio.ufop.br/handle/123456789/8608 |
dc.identifier.issn.none.fl_str_mv |
1383-5769 |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1016/j.parint.2016.07.005 |
identifier_str_mv |
DUARTE, M. C. et al. Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. Parasitology International, v. 65, p. 728-736, 2016. Disponível em: <http://www.sciencedirect.com/science/article/pii/S1383576916302240?via%3Dihub>. Acesso em: 29 ago. 2017. 1383-5769 |
url |
http://www.repositorio.ufop.br/handle/123456789/8608 https://doi.org/10.1016/j.parint.2016.07.005 |
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eng |
language |
eng |
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info:eu-repo/semantics/openAccess |
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UFOP |
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