IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
artículos
Título:
Antiparasitic Effect of Vitamin B12 on Trypanosoma cruzi
Autor/es:
ALEJANDRA B. CICCARELLI; FERNANDA M. FRANK; VANESA PUENTE; EMILIO L. MALCHIODI; ALCIRA BATLLE; MARIA ELISA LOMBARDO
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Lugar: Washington; Año: 2012 vol. 56 p. 5315 - 5320
ISSN:
0066-4804
Resumen:
A nutritional characteristic of trypanosomatid protozoa is that they need a heme compound as a growth factor. Because of the
cytotoxic activity of heme and its structural similarity to cobalamins, we have investigated the in vitro and in vivo effect of vitamin
B12 (or cyanocobalamin) on the different forms of Trypanosoma cruzi. Cyanocobalamin showed a marked antiparasitic activity
against epimastigotes (50% inhibitory concentration [IC50], 2.42 M), amastigotes (IC50, 10.69 M), and trypomastigotes
(IC50, 9.46 M). Anti-epimastigote and -trypomastigote values were 1.7 to 4 times lower than those obtained with the reference
drug benznidazole (Bnz). We also found that B12 and hemin do not interact with each other in their modes of action. Our results
show that B12 increases intracellular oxidative activity and stimulates both superoxide dismutase (50%) and ascorbate peroxidase
(20%) activities, while the activity of trypanothione reductase was not modified. In addition, we found that the antioxidants
dithiothreitol and ascorbic acid increase the susceptibility of the parasite to the cytotoxic action of B12. We propose that vitamin
B12 exerts its growth-inhibitory effect through the generation of reactive oxygen species. In an in vivo assay, a significant reduction
in the number of circulating parasites was found in T. cruzi-infected mice treated with cyanocobalamin and ascorbic acid.
The reduction of parasitemia in benznidazole-treated mice was improved by the addition of these vitamins. According to our
results, a combination of B12 and Bnz should be further investigated due to its potential as a new therapeutic modality for the
treatment of Chagas? disease.