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Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: e01722-18. doi: 10.1128/AAC.01722-18. Print 2019 Mar.

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

Author information

1
Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, São Paulo, Brazil.
2
Instituto de Física, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
3
Departamento de Biologia Geral, Universidade Estadual de Ponta Grossa, Paraná, Paraná, Brazil.
4
Grupo de Pesquisa em Ciências Naturais e Biotecnologia, Universidade Federal do Maranhão, Grajaú, Maranhão, Brazil.
5
Núcleo de Enteroparasitas, Instituto Adolfo Lutz, São Paulo, São Paulo, Brazil.
6
Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, São Paulo, Brazil josuem@usp.br.

Abstract

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.

KEYWORDS:

Schistosoma; antischistosomal compound; schistosomiasis; schitosomicidal activity; spironolactone

PMID:
30559137
DOI:
10.1128/AAC.01722-18

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