Benznidazole and aspirin association for the treatment of chronic experimental Trypanosoma cruzi infection

Abstract

The drugs nifurtimox (NFX) and benznidazole (BZN) have been used for the treatment of Chagas disease since the 1970s. Alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates the effect of the association benznidazole (BZN) with aspirin (ASA) for the treatment of experimental Chagas disease in the chronic stage. This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Brazilian National Council of Animal Experimentation (http://www.cobea.org.br/). The protocol was approved by the Committee on the Ethics of Animal Experiments at Londrina State University (CEEA, process number 4628.2016.40). To date, experiments were performed using 40 mice with 8 to 12 weeks old. Infected BALB/c mice with 5×103 by an intra‐peritoneal route were treated by gavage with ASA 25 mg/kg/day and BZN 25 mg/kg/day, each separately or together diluted in the drinking water. The drinking water was administered by gavage as a control for the potential impact of the stress associated with the daily handling associated with gavaging mice. The gavaging was initiated two days post‐infection (dpi) and parasitemia was performed using the Brener method on alternate days for 30 days from the third dpi. Efficacy of the treatment was evaluated through cardiovascular parameters, nitric oxide (NO) quantification in the plasma, cardiac tissue and spleen at 180 dpi. The treatments with BZN (25 mg/kg/day) alone or in association with ASA (25 mg/kg/day) significantly (P < 0.05) reduced mortality and decreased parasitemia. However, the mice treated with BZN and ASA combination maintained the levels of mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (HR) closer to the levels observed in control animals. While those of BZN group, had these parameters statistically increased. BZN combined with ASA showed an increase in NO production than mice treated only with BZN. Interesting, the treated with BZN and the ASA combination prevented heart enlargement characteristically observed in infected animals. The therapeutic results from the combination of BZN with ASA presented lesser side effects than the treatment with BZN.Support or Funding InformationThis work was supported by Programa Institucional de Pesquisa Básica e Aplicada, da Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Estado do Paraná,, Convênio 09/2016). BFCL, HTS and MILM received scholarships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). PPF, MCMP and SFYO received research fellowship from CNPq. RSP received scholarships from UniZambeze and MCTESTP Mozambique.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.