In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing.

Autor:	Guerra RA; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, São Paulo, Brazil., Silva MP; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, São Paulo, Brazil., Silva TC; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, São Paulo, Brazil., Salvadori MC; Instituto de Física, Universidade de São Paulo, São Paulo, São Paulo, Brazil., Teixeira FS; Instituto de Física, Universidade de São Paulo, São Paulo, São Paulo, Brazil., de Oliveira RN; Departamento de Biologia Geral, Universidade Estadual de Ponta Grossa, Paraná, Paraná, Brazil., Rocha JA; Grupo de Pesquisa em Ciências Naturais e Biotecnologia, Universidade Federal do Maranhão, Grajaú, Maranhão, Brazil., Pinto PLS; Núcleo de Enteroparasitas, Instituto Adolfo Lutz, São Paulo, São Paulo, Brazil., de Moraes J; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, São Paulo, Brazil josuem@usp.br.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Feb 26; Vol. 63 (3). Date of Electronic Publication: 2019 Feb 26 (Print Publication: 2019).
DOI:	10.1128/AAC.01722-18
Abstrakt:	Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoni in vitro and in vivo in a murine model of schistosomiasis. In vitro , spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death. In vivo , oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly ( P <  0.05 to P <  0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing. (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
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