| Author | Andrade Neto, Valter Viana | |
| Author | Pacheco, Juliana da Silva | |
| Author | Inácio, Job Domingos | |
| Author | Amaral, Elmo Eduardo Almeida | |
| Author | Santos, Eduardo Caio Torres | |
| Author | Cunha Junior, Edezio Ferreira | |
| Access date | 2021-04-30T18:26:07Z | |
| Available date | 2021-04-30T18:26:07Z | |
| Document date | 2021 | |
| Citation | ANDRADE NETO, Valter Viana et al. Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis. Front. Pharmacol., v. 12, Article 636265, 7p, Apr. 2021. | pt_BR |
| ISSN | 1663-9812 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/46986 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmaniose | pt_BR |
| Subject in Portuguese | Espironolactona | pt_BR |
| Subject in Portuguese | Reposicionamento de drogas | pt_BR |
| Subject in Portuguese | Leishmaniose visceral | pt_BR |
| Subject in Portuguese | Antimonial pentavalente | pt_BR |
| Title | Efficacy of Spironolactone treatment in murine models of Cutaneous and Visceral Leishmaniasis | pt_BR |
| Type | Article | |
| DOI | 10.3389/fphar.2021.636265 | |
| Abstract | Translational studies involving the reuse and association of drugs are approaches that
can result in higher success rates in the discovery and development of drugs for serious
public health problems, including leishmaniasis. If we consider the number of
pathogenic species in relation to therapeutic options, this arsenal is still small, and
each drug possesses a disadvantage in terms of toxicity, efficacy, price, or treatment
regimen. In the search for new drugs, we performed a drug screening of L.
amazonensis promastigotes and intracellular amastigotes of fifty available drugs
belonging to several classes according to their pharmacophoric group.
Spironolactone, a potassium-sparing diuretic, proved to be the most promising
drug candidate. After demonstrating the in vitro antileishmanial activity, we
evaluated the efficacy on a murine experimental model with L. amazonensis and L.
infantum. The treatment controlled the cutaneous lesion and reduced the parasite
burden of L. amazonensis significantly, as effectively as meglumine antimoniate. The
treatment of experimental visceral leishmaniasis was effective in reducing the parasite
load on the main affected organs (spleen and liver) via high doses of spironolactone.
The association between spironolactone and meglumine antimoniate promoted better
control of the parasite load in the spleen and liver compared to the group treated with
meglumine antimoniate alone. These results reveal a possible benefit of the concomitant use
of spironolactone and meglumine antimoniate that should be studied more in depth for the
future possibility of repositioning for leishmaniasis co-therapy. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil / University of Dundee. School of Life Sciences. Division of Biological Chemistry and Drug Discovery. Dundee, United Kingdom. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Laboratório de Imunoparasitologia, Unidade Integrada de Pesquisa em Produtos Bioativos e Biociencias. Campus UFRJ-Macaé. Macaé, RJ, Brasil. | pt_BR |
| Subject | Spironolactone | pt_BR |
| Subject | Drug repositioning | pt_BR |
| Subject | Leishmania | pt_BR |
| Subject | Visceral leishmaniasis | pt_BR |
| Subject | Pentavalent antimonial | pt_BR |
