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Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis

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...

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Autores principales: Andrade-Neto, Valter Viana, da Silva Pacheco, Juliana, Inácio, Job Domingos, Almeida-Amaral, Elmo Eduardo, Torres-Santos, Eduardo Caio, Cunha-Junior, Edezio Ferreira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077169/
https://www.ncbi.nlm.nih.gov/pubmed/33927619
http://dx.doi.org/10.3389/fphar.2021.636265
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author Andrade-Neto, Valter Viana
da Silva Pacheco, Juliana
Inácio, Job Domingos
Almeida-Amaral, Elmo Eduardo
Torres-Santos, Eduardo Caio
Cunha-Junior, Edezio Ferreira
author_facet Andrade-Neto, Valter Viana
da Silva Pacheco, Juliana
Inácio, Job Domingos
Almeida-Amaral, Elmo Eduardo
Torres-Santos, Eduardo Caio
Cunha-Junior, Edezio Ferreira
author_sort Andrade-Neto, Valter Viana
collection PubMed
description 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.
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spelling pubmed-80771692021-04-28 Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis Andrade-Neto, Valter Viana da Silva Pacheco, Juliana Inácio, Job Domingos Almeida-Amaral, Elmo Eduardo Torres-Santos, Eduardo Caio Cunha-Junior, Edezio Ferreira Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-04-13 /pmc/articles/PMC8077169/ /pubmed/33927619 http://dx.doi.org/10.3389/fphar.2021.636265 Text en Copyright © 2021 Andrade-Neto, da Silva Pacheco, Inácio, Almeida-Amaral, Torres-Santos and Cunha-Junior. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Andrade-Neto, Valter Viana
da Silva Pacheco, Juliana
Inácio, Job Domingos
Almeida-Amaral, Elmo Eduardo
Torres-Santos, Eduardo Caio
Cunha-Junior, Edezio Ferreira
Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
title Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
title_full Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
title_fullStr Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
title_full_unstemmed Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
title_short Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
title_sort efficacy of spironolactone treatment in murine models of cutaneous and visceral leishmaniasis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077169/
https://www.ncbi.nlm.nih.gov/pubmed/33927619
http://dx.doi.org/10.3389/fphar.2021.636265
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