Artículo
Clomipramine and Benznidazole act synergistically and ameliorate the outcome of experimental Chagas disease: In vivo and in vitro assessments
García, Mónica Cristina
; Ponce, Nicolás Eric
; Sanmarco, Liliana Maria
; Manzo, Ruben Hilario
; Jimenez Kairuz, Alvaro Federico
; Aoki, Maria del Pilar
Fecha de publicación:
06/2016
Editorial:
American Society for Microbiology
Revista:
Antimicrobial Agents and Chemotherapy
ISSN:
0066-4804
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Chagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the in vitro and in vivo anti-Trypanosoma cruzi effects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ. In vitro studies, carried out using a checkerboard technique on trypomastigotes (T. cruzi strain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety.
Palabras clave:
Chagas Disease Therapy
,
Trypanosoma Cruzi
,
Benznidazole
,
Clomipramine
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos(UNITEFA)
Articulos de UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Articulos de UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Citación
García, Mónica Cristina; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Manzo, Ruben Hilario; Jimenez Kairuz, Alvaro Federico; et al.; Clomipramine and Benznidazole act synergistically and ameliorate the outcome of experimental Chagas disease: In vivo and in vitro assessments; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 60; 6; 6-2016; 3700-3708
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