title: Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi.
abstract: Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and African trypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect of pentamidine in Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have shown that pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its might also block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescine de 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, but also the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflammation 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 and spermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate the utility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of new therapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to a well-known clinical profile, which could be an advantage over newly synthesized molecules that require more comprehensive trials prior to their clinical use.
authors.affiliation: Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: María V
authors.initials: MV
authors.lastname: Díaz
authors.affiliation: Laboratorio de Biología Molecular de Trypanosoma cruzi (LBMTC), Instituto de Investigaciones Médicas "Alfredo Lanari", CONICET-Universidad de Buenos Aires,, Argentina.
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Miranda
authors.affiliation: Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Campos-Estrada
authors.affiliation: Laboratorio de Biología Molecular de Trypanosoma cruzi (LBMTC), Instituto de Investigaciones Médicas "Alfredo Lanari", CONICET-Universidad de Buenos Aires,, Argentina.
authors.forename: Chantal
authors.initials: C
authors.lastname: Reigada
authors.affiliation: Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Maya
authors.affiliation: Laboratorio de Biología Molecular de Trypanosoma cruzi (LBMTC), Instituto de Investigaciones Médicas "Alfredo Lanari", CONICET-Universidad de Buenos Aires,, Argentina.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Pereira
authors.affiliation: Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Electronic address: rodlopez@u.uchile.cl.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López-Muñoz
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D004195:Disease Models, Animal; D006321:Heart / Q000469:parasitology; D018320:Leishmania major / Q000187:drug effects*; D008297:Male; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D010419:Pentamidine / Q000494:pharmacology*; D011073:Polyamines / Q000378:metabolism*; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D011073:Polyamines; D010419:Pentamidine
keywords: Chagas’ disease; Pentamidine; Polyamine transport; Trypanosoma cruzi