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Autor | Santos, Diego Moura | |
Autor | Petersen, Antonio Luis de Oliveira Almeida | |
Autor | Celes, Fabiana Santana | |
Autor | Borges, Valeria de Matos | |
Autor | Veras, Patrícia Sampaio Tavares | |
Autor | Oliveira, Camila Indiani de | |
Fecha de acceso | 2014-11-12T18:52:56Z | |
Fecha de disponibilización | 2014-11-12T18:52:56Z | |
Fecha de publicación | 2014 | |
Referencia | SANTOS, D. M. et al. Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3275, 2014. | pt_BR |
ISSN | 1935-2727 | |
URI | https://www.arca.fiocruz.br/handle/icict/8817 | |
Idioma | eng | pt_BR |
Editor | Public Library of Science | pt_BR |
Derechos de autor | open access | pt_BR |
Palabras clave en Portugués | Leishmaniose | pt_BR |
Palabras clave en Portugués | Leishmaniose cutânea | pt_BR |
Palabras clave en Portugués | Leishmaniose Tegumentar | pt_BR |
Palabras clave en Portugués | Leishmania (Viannia) braziliensis | pt_BR |
Palabras clave en Portugués | Saúde pública | pt_BR |
Título | Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis | pt_BR |
Tipo del documento | Article | pt_BR |
DOI | 10.1371/journal.pntd.0003275 | |
Resumen en Inglés | Background: Leishmaniasis remains a worldwide public health problem. The limited therapeutic options, drug toxicity and reports of resistance, reinforce the need for the development of new treatment options. Previously, we showed that 17- (allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.) amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis. Methodology/Principal findings: Exposure of axenic L. (V.) braziliensis promastigotes to 17-AAG resulted in direct dosedependent parasite killing. These results were extended to L. (V.) braziliensis-infected macrophages, an effect that was dissociated from the production of nitric oxide (NO), superoxide (O22) or inflammatory mediators such as TNF-a, IL-6 and MCP-1. The leishmanicidal effect was then demonstrated in vivo, employing BALB/c mice infected with L. braziliensis. In this model, 17-AAG treatment resulted in smaller skin lesions and parasite counts were also significantly reduced. Lastly, 17-AAG showed a similar effect to amphotericin B regarding the ability to reduce parasite viability. Conclusion/Significance: 17-AAG effectively inhibited the growth of L. braziliensis, both in vitro and in vivo. Given the chronicity of L. (V.) braziliensis infection and its association with mucocutaneous leishmaniasis, 17-AAG can be envisaged as a new chemotherapeutic alternative for cutaneous Leishmaniasis. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil | pt_BR |