Artículo

Ciccarelli, A.B.; Frank, F.M.; Puente, V.; Malchiodi, E.L.; Batlle, A.; Lombardo, M.E. "Antiparasitic effect of vitamin B12 on Trypanosoma cruzi" (2012) Antimicrobial Agents and Chemotherapy. 56(10):5315-5320
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Abstract:

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 μM), amastigotes (IC50, 10.69 μM), and trypomastigotes (IC50, 9.46 μM). 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. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Registro:

Documento: Artículo
Título:Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
Autor:Ciccarelli, A.B.; Frank, F.M.; Puente, V.; Malchiodi, E.L.; Batlle, A.; Lombardo, M.E.
Filiación:CIPYP (UBA-CONICET), Hospital de Clińicas José de San Mart́in, UBA, Buenos Aires, Argentina
Departamento de Microbiologiá, Facultad de Medicina, UBA, Buenos Aires, Argentina
Cat́edra de Inmunología, IDEHU (UBA-CONICET), UBA, Buenos Aires, Argentina
Departamento de Quiḿica Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina
Palabras clave:ascorbate peroxidase; ascorbic acid; benznidazole; cobalamin; cyanocobalamin; dithiothreitol; heme; hemin; reactive oxygen metabolite; superoxide dismutase; trypanothione reductase; amastigote; animal experiment; animal model; antimicrobial activity; antiparasitic activity; article; controlled study; cytotoxicity; drug mechanism; enzyme activity; epimastigote; female; growth inhibition; IC 50; in vitro study; in vivo study; male; mouse; nonhuman; parasitemia; priority journal; Trypanosoma cruzi; trypomastigote; Animals; Chagas Disease; Female; Male; Mice; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi; Vitamin B 12
Año:2012
Volumen:56
Número:10
Página de inicio:5315
Página de fin:5320
DOI: http://dx.doi.org/10.1128/AAC.00481-12
Título revista:Antimicrobial Agents and Chemotherapy
Título revista abreviado:Antimicrob. Agents Chemother.
ISSN:00664804
CODEN:AMACC
CAS:ascorbate peroxidase, 72906-87-7; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; benznidazole, 22994-85-0; cobalamin, 13408-78-1; cyanocobalamin, 53570-76-6, 68-19-9, 8064-09-3; dithiothreitol, 3483-12-3; heme, 14875-96-8; hemin, 16009-13-5; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; trypanothione reductase, 102210-35-5; Nitroimidazoles; Trypanocidal Agents; Vitamin B 12, 68-19-9; benzonidazole, 22994-85-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v56_n10_p5315_Ciccarelli

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Citas:

---------- APA ----------
Ciccarelli, A.B., Frank, F.M., Puente, V., Malchiodi, E.L., Batlle, A. & Lombardo, M.E. (2012) . Antiparasitic effect of vitamin B12 on Trypanosoma cruzi. Antimicrobial Agents and Chemotherapy, 56(10), 5315-5320.
http://dx.doi.org/10.1128/AAC.00481-12
---------- CHICAGO ----------
Ciccarelli, A.B., Frank, F.M., Puente, V., Malchiodi, E.L., Batlle, A., Lombardo, M.E. "Antiparasitic effect of vitamin B12 on Trypanosoma cruzi" . Antimicrobial Agents and Chemotherapy 56, no. 10 (2012) : 5315-5320.
http://dx.doi.org/10.1128/AAC.00481-12
---------- MLA ----------
Ciccarelli, A.B., Frank, F.M., Puente, V., Malchiodi, E.L., Batlle, A., Lombardo, M.E. "Antiparasitic effect of vitamin B12 on Trypanosoma cruzi" . Antimicrobial Agents and Chemotherapy, vol. 56, no. 10, 2012, pp. 5315-5320.
http://dx.doi.org/10.1128/AAC.00481-12
---------- VANCOUVER ----------
Ciccarelli, A.B., Frank, F.M., Puente, V., Malchiodi, E.L., Batlle, A., Lombardo, M.E. Antiparasitic effect of vitamin B12 on Trypanosoma cruzi. Antimicrob. Agents Chemother. 2012;56(10):5315-5320.
http://dx.doi.org/10.1128/AAC.00481-12