Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease
| Autor: | Sérgio Caldas, Maria Terezinha Bahia, Ivo Santana Caldas, Tassiane Assíria Fontes Martins, Isabel Mayer de Andrade, Álvaro Fernando da Silva do Nascimento, Lívia de Figueiredo Diniz, Isabela Ribeiro, Ana Lia Mazzeti |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Drug
Chagas disease Combination therapy Itraconazole Science media_common.quotation_subject Trypanosoma cruzi Antibodies Protozoan Biology Pharmacology Parasite Load Mice Pharmacotherapy medicine Animals Chagas Disease Nifurtimox media_common Multidisciplinary Myocardium medicine.disease Trypanocidal Agents Drug repositioning Disease Models Animal Benznidazole Nitroimidazoles Immunoglobulin G Immunology Medicine Drug Therapy Combination Female medicine.drug Research Article |
| Zdroj: | PLoS ONE Repositório Institucional da UFOP Universidade Federal de Ouro Preto (UFOP) instacron:UFOP PLoS ONE, Vol 10, Iss 6, p e0128707 (2015) |
| ISSN: | 1932-6203 |
| Popis: | The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease. |
| Databáze: | OpenAIRE |
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