3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi

Abstract

Trypanosoma evansi is a pathogenic trypanosomatid with world distribution, which may cause big economic losses and affect almost all mammalian species. One of the most affected species is horses, which may develop a disease known as Mal das cadeiras. There are several clinical signs and pathologies resulting from this parasite infection. The acute phase is characterized by intermittent fever, subcutaneous edema, progressive anemia, blindness, lethargy and hemostatic abnormalities. In the chronic phase, animals exhibit cachexia, edema, incoordination and paralysis. The most common treatment for this infection is the use of drugs; however, these drugs have a moderate efficacy, and they may present toxicity, especially to kidney and liver. Thus, it is important to study new therapies for the treatment of the disease caused by T. evansi. The aim of this study was to investigate the anti-trypanosomal effect of the treatment with 3‟deoxyadenosine (cordycepin - adenosine analogue) combined with deoxycoformycin (pentostatin - inhibitor of the adenosine deaminase (ADA) enzyme and deoxyadenosine analogue) in mice experimentally infected with T. evansi. Furthermore, we also verified the influence of the therapy in the hematologic, biochemical and ADA activity parameters, makers of cell viability and toxicity, oxidative stress and histopathology analyses. These analyses were divided into three experiments. The first one showed that the combination of cordycepin (2mgkg-1) and pentostatin (2mgkg-1) was 100% effective in the T. evansi-infected groups; however, the treatment increased significantly the liver enzyme levels, which were accompanied by histological lesions in the liver and kidneys. The second experiment showed a reduction in the levels of plasma total protein in healthy mice and treated with 1mg/kg cordycepin or 1mg/kg pentostatin. The animals treated with pentostatin alone or associated with cordycepin showed an ADA activity significantly reduced. The third experiment showed that the combination of cordycepin (2.0 mg kg-1) and pentostatin (0.2, 0.5, 1.0, 2.0 mg kg-1) is effective in the clearance of T. evansi, although at higher concentrations (cordycepin 2mg kg-1 and pentostatin 2mg kg-1), toxicity was observed. Therefore, the dose cordycepin 2.0 mg kg-1 in combination with pentostatin 0.2 mg kg-1 was recommended as a therapeutic option. This combination showed to be 100% effective in the experimentally infected animals and presented no toxicity to the animals.