What is it about?

The enclosed report represents an important contribution to current scientific knowledge of antichagasic compounds. Endemic throughout Latin America, Chagas disease is estimated to kill 14,000 people every year. Despite the large number of patient infected with Trypanosoma cruzi, there are no commercial drugs available with high efficacy. In this work, we comprehensively evaluated the in vitro and in vivo anti-T. cruzi effect of clomipramine (a parasite-trypanothione reductase specific inhibitor) and benznidazole combination, in order to design new alternative strategies aimed to improve the current etiological treatments

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Why is it important?

Although many compounds might show promising activity against T. cruzi, the little standardization among the protocols employed has limited further studies. Through in vitro studies, carried out by checkerboard technique, we verified the synergistic effect of the combination on trypomastigote viability. In addition, the results obtained from in vitro assays together with the analysis of pharmacokinetic parameters and allometric approaches; allowed us to purpose the range of doses for in vivo experiments. This strategy was highly effective to reduce the amount of animals employed in these studies.

Perspectives

The therapy with clomipramine combined with lower doses of benznidazole reduced cardiac inflammation and improved the outcome of the chronic cardiomyopathy in comparison with the clinical doses of benznidazole. Summing up our results clearly evidenced a synergic activity of benznidazole-clomipramine combination for the potential treatment of Chagas disease.

Dr. Maria P Aoki
Universidad Nacional de Cordoba

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This page is a summary of: Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease, Antimicrobial Agents and Chemotherapy, April 2016, ASM Journals,
DOI: 10.1128/aac.00404-16.
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