DEOXYADENOSINE AND DEOXYCOFORMYCIN FOR THE TREATMENT OF TRYPANOSOMA EVANSI INFECTION
Autor(es): LUCIANA DALLA ROSA, ALEKSANDRO S. DA SILVA, CAMILA B. OLIVEIRA, LUCAS T. GRESSLER, CAROLINE B. ARNOLD, MATHEUS D. BALDISSERA, MICHELE SAGRILLO, IVANA B. M. CRUZ, MANUELA SANGOI, RAFAEL MORESCO, RICARDO E. MENDES, PAULO E. WEISS, LUIZ C. MILETTI, SILVIA G. MONTEIRO
DEOXYADENOSINE AND DEOXYCOFORMYCIN FOR THE TREATMENT OF TRYPANOSOMA EVANSI INFECTION
» Área de pesquisa: PROTOZOOLOGIA
» Instituição: Universidade Federal de Santa Maria
» Agência de fomento e patrocinadores: CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Trypanosoma evansi is a flagellated protozoan causes a devastating disease in a huge range of hosts, and is the most prevalent pathogenic trypanosome throughout the tropical and subtropical areas of the world. Clinically, infection is characterized by rapid weight loss, various degrees of anemia, intermittent fever, edema of the hind limbs, progressive weakness and locomotor disturbance, eventually leading to death. To date, several drugs have been used for the treatment of T. evansi infection, yet their efficacy and toxicity have proven to be problematic. Moreover, in some instances drug resistance has been reported. Thus, it is important to investigate alternative therapies for the treatment of T. evansi. Importantly, one characteristic of trypanosomes is their inability to engage in de novo purine synthesis. In particular, their dependence on the nucleoside salvage pathway from the body fluids of their hosts has been exploited as a therapeutic target. The aim of this study was to evaluate the therapeutic efficacy and viability of using 3′deoxyadenosine (Cordycepin - adenosine analogue) combined with deoxycoformycin (Pentostatin – an adenosine deaminase inhibitor) in mice infected with Trypanosoma evansi. We show 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), some toxicity was observed in the liver, kidney and spleen. Since the Cordycepin 2.0 mg kg-1 and Pentostatin 0.2 mg kg-1 combination was effective and had low toxicity, we recommend this as a therapeutic option. Therefore, we conclude that when combined, Cordyceptin and Pentostatin are able to effectively eliminate T. evansi.
