Eflornithine potentiates the action of benznidazole on two strains of Trypanosoma cruzi.

ROMANO PS; MARTINEZ SJ

Mendoza

Simposio; II International Symposium of Traslational Medicine; 2019

Facultad de Ciencias Médicas. UNCUYO

Introduction: finding an effective therapy against Chagas disease is one of the research priorities of the WHO, which is expanding a global action to eliminate this illness since 2007. Up to date, the only drugs approved against T. cruzi are Benznidazole (BNZ) and Nifurtimox, which have positive results for the acute phase, but with relative efficacy in the chronic phase besides its very unpleasant side effects. Aims: our strategy was to identify a new drug which combined with BNZ increased the effectiveness and, at the same time, reduced the noxious dose of BNZ. Based in our previously published data, we proposed the incorporation of Eflornithine (DFMO) to the current treatment of BNZ. Methods: we performed experiments on T. cruzi epimastigotes and intracellular amastigotes treated with increasing concentrations of BNZ (1 to 100M) in the presence or not of DFMO (1 to 10mM) and compared to control. These experiments were done for both, a DTU TcII T. cruzi strain and a DTU TcV strain recently isolated from a chronic patient in our laboratory. Results: our data showed significant differences between the IC50 values obtained in epimastigotes and also in the intracellular replication of amastigotes in rat myocardium cells from both strains. We also observed an important reduction in the IC50 value for the combined therapy compared to BNZ treatment alone. Conclusion: both DTUs displayed significant differences in the susceptibility to BNZ, being TcII more resistant than TcV, and a better effectiveness of the combined treatment. We also highlight the positive effect of DFMO as a possible adjuvant drug for Chagas disease therapy.