Some of anti-parasitic agents have also shown the capacity to promote different PCD phenotypes in distinct morphological forms of Leishmania sp. ( Monte Neto et al., 2011; Schurigt et al., 2010) and T. cruzi ( Menna-Barreto et al., 2009; Sandes et al., 2010), as was observed with the use of naphthoimidazoles against T. cruzi epimastigotes and trypomastigotes ( Menna-Barreto et al., 2009). Our current results with the melittin peptide, together with the published crude A. mellifera venom data, agree with the

concept that the same compound can generate different ABT-737 manufacturer cell death phenotypes. The lytic effect of melittin on red blood cell membranes has made it an unlikely therapeutic for human use (Blondelle and Houghten, 1991). The ability of melittin to bind to cell membranes is dependent on the phospholipid composition of the membrane, which may confer some selectivity to the effect of the AMP (Raghuraman

and Chattopadhyay, 2007). For this reason, the ability of melittin to affect eukaryotic cell membranes was evaluated prior to determining the effects of the peptide on T. cruzi intracellular forms. Our results confirm that melittin as a single peptide can be used to treat infected host cells in vitro at low concentrations (up to 1 μg/ml). However, previous Oligomycin A supplier studies have shown that low concentrations of melittin, or its use as a hybrid with other AMPs, present low toxicity to mammalian cells ( Alberola et al., 2004; Chicharro et al., 2001; Díaz-Achirica et al., 1998; Jacobs et al., C1GALT1 2003; Luque-Ortega et al., 2001, 2003; Seeber, 2000; Wade et al., 1990; Boman et al., 1989). Because melittin was

effective against the amastigote forms, we believe that a hybrid melittin compound may be employed in future in vitro and in vivo Chagas disease chemotherapies. Chagas disease is an important but neglected disease whose eradication is hampered by inefficient treatment regimens, growing oral transmission within endemic countries and global spread via the emigration of infected people. The ideal drug for the treatment of chagasic patients must be capable of killing the T. cruzi parasite without triggering host defenses. AMPs are a component of the innate immune response of organisms in virtually every kingdom and phylum found worldwide. More importantly, they represent a great source of compounds for drug development because they carry a low likelihood of resistance development and display a rapid mode of action. Our findings demonstrate that all T. cruzi developmental forms were susceptible to the melittin peptide and that distinct PCD phenotypes were detected in different forms of treated parasites.