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Wasp venom peptide as a new antichagasic agent

2020; Elsevier BV; Volume: 181; Linguagem: Inglês

10.1016/j.toxicon.2020.04.099

1879-3150

Katielle Albuquerque Freire, Marcelo D. T. Torres, Dânya Bandeira Lima, Marília Lopes Monteiro, Ramon Róseo Paula Pessoa Bezerra de Menezes, Alice Maria Costa Martins, Vani Xavier Oliveira,

Trypanosoma species research and implications

Chagas disease is caused by Trypanosoma cruzi and affects approximately 10 million people a year worldwide. The only two treatment options, benznidazole and nifurtimox, have low efficacy and high toxicity towards human cells. Mastoporan peptide (MP) a small cationic AMP from the venom of the wasp Polybia paulista has been reported as a potent trypanocidal agent. Thus, we evaluated the antichagasic effect of another AMP from the venom of the same wasp Polybia paulista, polybia-CP (ILGTILGLLSKL-NH2), and investigated its mechanism of action against different stages of the trypanosomal cells life cycle. Polybia-CP was tested against the epimastigote, trypomastigote and amastigote forms of the T. cruzi Y strain (benznidazole-resistant strain) and inhibited the development of these forms. We also assessed the selectivity of the AMP against mammalian cells by exposing LLC-MK2 cells to polybia-CP, the peptide presented a high selectivity index (>106). The mechanism of action of polybia-CP on trypanosomal cells was investigated by flow cytometry, scanning electron microscopy (SEM) and enzymatic assays with T. cruzi GAPDH (tcGAPDH), enzyme that catalyzes the sixth step of glycolysis. Polybia-CP induced phosphatidylserine exposure, it also increased the formation of reactive species of oxigen (ROS) and reduced the transmembrane mitochondrial potential. Polybia-CP also led to cell shrinkage, evidencing apoptotic cell death. We did not observe the inhibition of tcGAPDH or autophagy induction. Altogether, polybia-CP has shown the features of a promising template for the development of new antichagasic agents.