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In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>anti-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma cruzi<\/jats:named-content>effects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ.<jats:italic>In vitro<\/jats:italic>studies, carried out using a checkerboard technique on trypomastigotes (<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>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.<\/jats:p>","DOI":"10.1128\/aac.00404-16","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T03:39:01Z","timestamp":1460432341000},"page":"3700-3708","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease"],"prefix":"10.1128","volume":"60","author":[{"given":"M\u00f3nica Cristina","family":"Garc\u00eda","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n y Desarrollo en Tecnolog\u00eda Farmac\u00e9utica (UNITEFA), CONICET, and Departamento de Farmacia, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicol\u00e1s Eric","family":"Ponce","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), CONICET, and Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana Maria","family":"Sanmarco","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), CONICET, and Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n Hilario","family":"Manzo","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n y Desarrollo en Tecnolog\u00eda Farmac\u00e9utica (UNITEFA), CONICET, and Departamento de Farmacia, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro Federico","family":"Jimenez-Kairuz","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n y Desarrollo en Tecnolog\u00eda Farmac\u00e9utica (UNITEFA), CONICET, and Departamento de Farmacia, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pilar","family":"Aoki","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), CONICET, and Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Chagas disease","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. 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