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Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin, found in Crotalus durissus terrificus rattlesnake's venom gland

Published online by Cambridge University Press:  06 December 2017

Izabel Cristina Justino Bandeira
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Danya Bandeira-Lima
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Clarissa Perdigão Mello
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Ticiana Praciano Pereira
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Ramon Róseo Paula Pessoa Bezerra De Menezes
Affiliation:
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Tiago Lima Sampaio
Affiliation:
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Cláudio Borges Falcão
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Gandhi Rádis-Baptista*
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil Instituto de Ciências do Mar, Universidade Federal do Ceara, Fortaleza, CE, Brasil
Alice Maria Costa Martins*
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
*
Authors for correspondence: Alice Maria Costa Martins, E-mail: martinsalice@gmail.com; Gandhi Rádis-Baptista, E-mail: radisbra@yahoo.com
Authors for correspondence: Alice Maria Costa Martins, E-mail: martinsalice@gmail.com; Gandhi Rádis-Baptista, E-mail: radisbra@yahoo.com

Abstract

Cathelicidins are antimicrobial peptides produced by humans and animals in response to various pathogenic microbes. Crotalicidin (Ctn), a cathelicidin-related vipericidin from the South American Crotalus durissus terrificus rattlesnake's venom gland, and its fragments have demonstrated antimicrobial and antifungal activity, similarly to human cathelicidin LL-37. In order to provide templates for the development of modern trypanocidal agents, the present study evaluated the antichagasic effect of these four peptides (Ctn, Ctn[1-14], Ctn[15-34] and LL-37). Herein, Ctn and short derived peptides were tested against the epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi Y strain (benznidazole-resistant strain) and cytotoxicity in mammalian cells was evaluated against LLC-MK2 lineage cells. Ctn inhibited all T. cruzi developmental forms, including amastigotes, which is implicated in the burden of infection in the chronic phase of Chagas disease. Moreover, Ctn showed a high selective index against trypomastigote forms (>200). Ctn induced cell death in T. cruzi through necrosis, as determined by flow cytometry analyses with specific molecular probes and morphological alterations, such as loss of membrane integrity and cell shrinkage, as observed through scanning electron microscopy. Overall, Ctn seems to be a promising template for the development of antichagasic agents.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2017 

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Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin, found in Crotalus durissus terrificus rattlesnake's venom gland
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Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin, found in Crotalus durissus terrificus rattlesnake's venom gland
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