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

Autor(es)

Guerra, Rafael A. ^[1] ; Silva, Marcos P. ^[1] ; Silva, Tais C. ^[1] ; Salvadori, Maria C. ^[2] ; Teixeira, Fernanda S. ^[2] ; de Oliveira, Rosimeire N. ^[3] ; Rocha, Jefferson A. ^[4] ; Pinto, Pedro L. S. ^[5] ; de Moraes, Josue ^[1]

Afiliação do(s) autor(es)

^[1] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, Guarulhos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis, Sao Paulo, SP - Brazil

^[3] Univ Estadual Ponta Grossa, Dept Biol Geral, Ponta Grossa, Parana - Brazil

^[4] Univ Fed Maranhao, Grp Pesquisa Ciencias Nat & Biotecnol, Grajau, Maranhao - Brazil

^[5] Adolfo Lutz Inst, Nucleo Enteroparasitas, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Antimicrobial Agents and Chemotherapy; v. 63, n. 3 MAR 2019.
• Citações Web of Science: 2

Resumo

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 mu M) 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. (AU)

• Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular