Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/35351 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil. |
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Rebello, Karina M.Andrade Neto, Valter V.Gomes, Claudia Regina B.Souza, Marcos Vinícius N. deBranquinha, Marta H.Santos, André L. S.Santos, Eduardo Caio Torresd`Avila-Levy, Claudia M.2019-09-05T13:29:54Z2019-09-05T13:29:54Z2019REBELLO, Karina M. et al. Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches. Frontiers in Cellular and Infection MIcrobiology, v. 9, p. 1-8, June 2019.2235-2988https://www.arca.fiocruz.br/handle/icict/3535110.3389/fcimb.2019.00229engFrontiers MediaHIVCo-infecçãoQuimioterapiaTratamentoLeishmanioseChemotherapyCo-infectionHIVHIV-PILeishmaniasisTreatmentMiltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approachesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Síntese de Substâncias no Combate a Doenças Tropicais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Síntese de Substâncias no Combate a Doenças Tropicais. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.Concurrently, leishmaniasis and AIDS are global public health issues and the overlap between these diseases adds additional treats to the management of co-infected patients. Lopinavir (LPV) has a well characterized anti-HIV and leishmanicidal action, and to analyze its combined action with miltefosine (MFS) could help to envisage strategies to the management of co-infected patients. Here, we evaluate the interaction between LPV and MFS against Leishmania infantum infection by in vitro and in vivo approaches. The effect of the compounds alone or in association was assessed for 72 h in mouse peritoneal macrophages infected with L. infantum by the determination of the IC50s and FICIs. Subsequently, mice were orally treated twice daily during 5 days with the compounds alone or in association and evaluated after 30 days. The in vitro assays revealed an IC50 of 0.24 μM and 9.89 μM of MFS and LPV, respectively, and an additive effect of the compounds (FICI 1.28). The in vivo assays revealed that LPV alone reduced the parasite load in the spleen and liver by 52 and 40%, respectively. The combined treatment of infected BALB/c mice revealed that the compounds alone required at least two times higher doses than when administered in association to virtually eliminate the parasite. Mice plasma biochemical parameters assessed revealed that the combined therapy did not present any relevant hepatotoxicity. In conclusion, the association of MFS with LPV allowed a reduction in each compound concentration to achieve the same outcome in the treatment of visceral leishmaniasis. Although a pronounced synergistic effect was not evidenced, it does not discard that such combination could be useful in humans co-infected with HIV and Leishmania parasites.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/35351/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALKarinaRebello_ClaudiaMLevy_etal_IOC_2019.pdfKarinaRebello_ClaudiaMLevy_etal_IOC_2019.pdfapplication/pdf1447207https://www.arca.fiocruz.br/bitstream/icict/35351/2/KarinaRebello_ClaudiaMLevy_etal_IOC_2019.pdf953ae8b6393c6500175c5aca485c5210MD52TEXTKarinaRebello_ClaudiaMLevy_etal_IOC_2019.pdf.txtKarinaRebello_ClaudiaMLevy_etal_IOC_2019.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| title |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| spellingShingle |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches Rebello, Karina M. HIV Co-infecção Quimioterapia Tratamento Leishmaniose Chemotherapy Co-infection HIV HIV-PI Leishmaniasis Treatment |
| title_short |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| title_full |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| title_fullStr |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| title_full_unstemmed |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| title_sort |
Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches |
| author |
Rebello, Karina M. |
| author_facet |
Rebello, Karina M. Andrade Neto, Valter V. Gomes, Claudia Regina B. Souza, Marcos Vinícius N. de Branquinha, Marta H. Santos, André L. S. Santos, Eduardo Caio Torres d`Avila-Levy, Claudia M. |
| author_role |
author |
| author2 |
Andrade Neto, Valter V. Gomes, Claudia Regina B. Souza, Marcos Vinícius N. de Branquinha, Marta H. Santos, André L. S. Santos, Eduardo Caio Torres d`Avila-Levy, Claudia M. |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Rebello, Karina M. Andrade Neto, Valter V. Gomes, Claudia Regina B. Souza, Marcos Vinícius N. de Branquinha, Marta H. Santos, André L. S. Santos, Eduardo Caio Torres d`Avila-Levy, Claudia M. |
| dc.subject.other.pt_BR.fl_str_mv |
HIV Co-infecção Quimioterapia Tratamento Leishmaniose |
| topic |
HIV Co-infecção Quimioterapia Tratamento Leishmaniose Chemotherapy Co-infection HIV HIV-PI Leishmaniasis Treatment |
| dc.subject.en.pt_BR.fl_str_mv |
Chemotherapy Co-infection HIV HIV-PI Leishmaniasis Treatment |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil. |
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2019 |
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2019-09-05T13:29:54Z |
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2019-09-05T13:29:54Z |
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2019 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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REBELLO, Karina M. et al. Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches. Frontiers in Cellular and Infection MIcrobiology, v. 9, p. 1-8, June 2019. |
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https://www.arca.fiocruz.br/handle/icict/35351 |
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2235-2988 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fcimb.2019.00229 |
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REBELLO, Karina M. et al. Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches. Frontiers in Cellular and Infection MIcrobiology, v. 9, p. 1-8, June 2019. 2235-2988 10.3389/fcimb.2019.00229 |
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