H1-antihistamines as antischistosomal drugs: in vitro and in vivo studies.

Autor: Xavier RP; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil., Mengarda AC; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil., Silva MP; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil., Roquini DB; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil., Salvadori MC; Instituto de Física, Universidade de São Paulo, São Paulo, SP, Brazil., Teixeira FS; Instituto de Física, Universidade de São Paulo, São Paulo, SP, Brazil., Pinto PL; Núcleo de Enteroparasitas, Instituto Adolfo Lutz, São Paulo, SP, Brazil., Morais TR; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil., Ferreira LLG; Laboratório de Química Medicinal e Computacional, Instituto de Física de São Carlos, Universidade de São Paulo, São Paulo, SP, Brazil., Andricopulo AD; Laboratório de Química Medicinal e Computacional, Instituto de Física de São Carlos, Universidade de São Paulo, São Paulo, SP, Brazil., de Moraes J; Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil. moraesnpdn@gmail.com.
Jazyk: angličtina
Zdroj: Parasites & vectors [Parasit Vectors] 2020 Jun 01; Vol. 13 (1), pp. 278. Date of Electronic Publication: 2020 Jun 01.
DOI: 10.1186/s13071-020-04140-z
Abstrakt: Background: Schistosomiasis is a socioeconomically devastating parasitic infection afflicting hundreds of millions of people and animals worldwide. It is the most important helminth infection, and its treatment relies solely on the drug praziquantel. Oral H1-antihistamines are available worldwide, and these agents are among the most widely used of all medications in children and adults. Given the importance of the drug repositioning strategy, we evaluated the antischistosomal properties of the H1-antihistamine drugs commonly used in clinical practices.
Methods: Twenty-one antihistamine drugs were initially screened against adult schistosomes ex vivo. Subsequently, we investigated the anthelmintic properties of these antihistamines in a murine model of schistosomiasis for both early and chronic S. mansoni infections at oral dosages of 400 mg/kg single dose or 100 mg/kg daily for five consecutive days. We also demonstrated and described the ability of three antihistamines to induce tegumental damage in schistosomes through the use of scanning electron microscopy.
Results: From phenotypic screening, we found that desloratadine, rupatadine, promethazine, and cinnarizine kill adult S. mansoni in vitro at low concentrations (5-15 µM). These results were further supported by scanning electron microscopy analysis. In an animal model, rupatadine and cinnarizine revealed moderate worm burden reductions in mice harboring either early or chronic S. mansoni infection. Egg production, a key mechanism for both transmission and pathogenesis, was also markedly inhibited by rupatadine and cinnarizine, and a significant reduction in hepatomegaly and splenomegaly was recorded. Although less effective, desloratadine also revealed significant activity against the adult and juvenile parasites.
Conclusions: Although the worm burden reductions achieved are all only moderate, comparatively, treatment with any of the three antihistamines is more effective in early infection than praziquantel. On the other hand, the clinical use of H1-antihistamines for the treatment of schistosomiasis is highly unlikely.
Databáze: MEDLINE
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