Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activityand inhibits the polyamine transport in Trypanosoma cruzi

Abstract

Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and Africantrypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect ofpentamidine in Trypanosoma cruzi, the etiological agent of Chagas’ disease. Recent studies have shownthat pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its mightalso block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescinede novo, the inhibition of polyamine transport can bring a new therapeutic target against the parasite.In this work, we show that pentamidine decreases, not only the viability of T. cruzi trypomastigotes, butalso the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflam-mation and parasite burden in hearts from infected mice. The treatment also decreases parasitemia,resulting in an increased survival rate. In addition, pentamidine strongly inhibits the putrescine andspermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate theutility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of newtherapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to awell-known clinical profile, which could be an advantage over newly synthesized molecules that requiremore comprehensive trials prior to their clinical use.