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Ex-vivo evaluation of antimalarial effects of violacein in amazonian isolates of Plasmodium vivax and P. falciparum and analysis of its activity in mice infected with resistant strains of P. chabaudi

Author(s):
Isabel Cristina Naranjo Prado
Total Authors: 1
Document type: Master's Dissertation
Institution: Universidade Estadual de Campinas. Instituto de Biologia
Defense date:
Examining board members:
Marcelo Brocchi; Pedro Vitor Lemos Cravo
Advisor: Fabio Trindade Maranhão Costa
Abstract

Malaria is responsible for about 300 million infections and one million deaths per year. In Brazil in 2012, about 1500 cases were reported and malaria vivax accounts for 85% of these. Still, it is frequently reported treatment failure with conventional antimalarials (as chloroquine and mefloquine) mainly in infections with P. falciparum but also by P. vivax parasite. Because of that combination therapies with artemisinin and its derivatives (ACT) are now currently recommended. In a previous work, our group demonstrated that violacein was able to inhibit the in vitro growth of laboratory strains of P. falciparum and also to strongly control the parasitemia of mice infected with P. chabaudi. This project aims to investigate further the antimalarial activity of violacein evaluating its activity in Amazonian isolates of P. falciparum recently adapted in culture, and in P. vivax isolates immediately after collecting blood from infected patients. Furthermore, we investigate the potential of violacein as combination therapy with artesunate in the treatment of murine strains which are resistant in different levels to artesunate, mefloquine and chloroquine. The antimalarial activity of violacein were initially investigated in vitro against P. falciparum 3D7 using two different types of violacein, one comercial, extracted from Janthinobacterium lividum (vJl-IC50: 227 nM), and another extracted from Chromobacterium violaceum (vCv-IC50: 390 nM) by our collaborators. In spite of no difference in the antimalarial activity between the two violaceins, the one extracted from C. violaceum had the lowest toxicity in erythrocytes (<400 nM) and in human hepatoma cells (<800 nM). Because of this, the antimalarial activity only of vCv was evaluated against 7 field isolates of P. falciparum showing a similar IC50 to that found for P. falciparum 3D7 (IC50= 419.8 nM). The antimalarial activity was also evaluated in murine strains of P. chabaudi showing a significant (P < 0.05) parasitemia decrease in the peak day in the two clones of P. chabaudi tested, one resistant to chloroquine (30CQ) and another resistant to artesunate and mefloquine (ATNMF1). Additionally, in P. vivax vCv was capable to reduce the parasite maturation in the four isolates tested. Therefore we can conclude that the vCv has an antimalarial effect on field isolates of P. falciparum and can be especially useful when used in combination with artesunate in the treatment of mice infected with resistant strains. Moreover, more assays should be conducted using blood infected with P. vivax to corroborate its effect in inhibiting the maturation of trophozoites. (AU)

FAPESP's process: 12/01892-0 - Evaluation of violacein antimalarial effect on Plasmodium vivax and P. falciparum isolates from Brazilian Amazon and analysis of violacein activity on P. chabaudi multi-drug resistant infected mice
Grantee:Isabel Cristina Naranjo Prado
Support type: Scholarships in Brazil - Master