Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi

Abstract

Discovered more than 100 years ago by the brazilian doctor Carlos Justiniano Ribeiro das Chagas (1879-1934), Chagas disease, also known as American trypanosomiasis, whose etiological agent is the protozoan Trypanosoma cruzi, is among the main Neglected Tropical Diseases (NTDs). Currently, the drugs available on the market are Benznidazole and Nifurtimox, developed in the 1970s, effective in the acute phase, however, both have their effectiveness reduced as the time of infection increases and adverse reactions become more frequent. This scenario is a major contributor to the scientific community to seek new alternatives and possible strategies for the treatment of this disease. This work aims to evaluate the effects of the combination of Levamisole and Lansoprazole on epimastigote forms of Dm28c strain of T. cruzi. Levamisole is a drug commonly used as an anthelmintic and has potent immunomodulatory activity. Lansoprazole is a gastric proton pump inhibitor, advised for healing and symptomatic relief of reflux esophagitis. Based on data recently obtained by LabImunoBio (UFMS), the drug Lansoprazole shows biological activity against different life forms of T.cruzi Dm28c, and has therefore become a promising target for drug repositioning studies. Combination tests were then carried out using different concentrations of both drugs. From this, the cell viability of the parasites was analyzed by observation and determined using the MTS assay. With the calculation of viability and inhibitory concentrations, we aimed to determine the classification according to Chou (2006), as follows: strong synergism; synergism; moderate synergism; and almost additive, so that the best combination between the two drugs could be evaluated by determining the combination index of the best association. Finally, the results of this work highlight the 3:1 ratio where its inhibitory concentrations had a better value in comparison to the others.