Possible treatments against Trypanosoma cruzi through the combined use of Trypanocidal drugs

NARDELLA GONZALO NICOLÁS; MARTINEZ SANTIAGO JOSE; ROMANO PATRICIA SILVIA

Córdoba

Congreso; 52 th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2016

Sociedad Argentina de Investigación en Bioquímica y Biologia Molecular

Chagas is an American endemic disease caused by the protozoan Trypanosoma cruzi, whose current therapy involves ineffective and unspecific treatments that cause serious side effects. Benznidazole (BNZ) and Nifurtimox are still the only drugs recommended up to date. These drugs require prolonged treatment, have limited efficacy in the chronic phase and against different T. cruzi strains. There is an urgent necessity to discover new therapeutic targets and new anti-chagasic drugs. In this work, we studied the effect of Difluoro-Methyl-ornithine (DFMO or eflornithine), an ornithine decarboxylase inhibitor that decrease the polyamine levels in Trypanosoma brucei, the etiologic agent of sleeping sickness and in mammalian cells. While DFMO has not significant effects on T. cruzi (TC II) alone, we detected significant trypanocidal action in the BNZ and DFMO combined therapy at concentrations of 100 μM and 5 mM respectively. In contrast, in the same assays, BNZ displayed trypanostatic activity. Furthermore, a reduced number of intracellular amastigotes was observed in the samples treated with both drugs. This result opens the way to reconsider the current dosage of BNZ treatment for Chagas disease.