Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8817
Title: Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
Authors: Santos, Diego Moura
Petersen, Antonio Luis de Oliveira Almeida
Celes, Fabiana Santana
Borges, Valeria de Matos
Veras, Patrícia Sampaio Tavares
Oliveira, Camila Indiani de
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
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
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
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
Abstract: 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.
keywords: Leishmaniose
Leishmaniose cutânea
Leishmaniose Tegumentar
Leishmania (Viannia) braziliensis
Saúde pública
Issue Date: 2014
Publisher: Public Library of Science
Citation: 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.
DOI: 10.1371/journal.pntd.0003275
ISSN: 1935-2727
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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