Antiparasitic effect of vitamin B12 on Trypanosoma cruzi

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 differen...

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Autores principales:	Ciccarelli, A.B., Frank, F.M., Puente, V., Malchiodi, E.L., Batlle, A., Lombardo, M.E.
Formato:	JOUR
Materias:	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 Vitamin B 12
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00664804_v56_n10_p5315_Ciccarelli
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00664804_v56_n10_p5315_Ciccarelli2023-10-03T14:53:05Z Antiparasitic effect of vitamin B12 on Trypanosoma cruzi Ciccarelli, A.B. Frank, F.M. Puente, V. Malchiodi, E.L. Batlle, A. Lombardo, M.E. 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 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. Fil:Ciccarelli, A.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lombardo, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00664804_v56_n10_p5315_Ciccarelli
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Ciccarelli, A.B. Frank, F.M. Puente, V. Malchiodi, E.L. Batlle, A. Lombardo, M.E. Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
topic_facet	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
description	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.
format	JOUR
author	Ciccarelli, A.B. Frank, F.M. Puente, V. Malchiodi, E.L. Batlle, A. Lombardo, M.E.
author_facet	Ciccarelli, A.B. Frank, F.M. Puente, V. Malchiodi, E.L. Batlle, A. Lombardo, M.E.
author_sort	Ciccarelli, A.B.
title	Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
title_short	Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
title_full	Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
title_fullStr	Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
title_full_unstemmed	Antiparasitic effect of vitamin B12 on Trypanosoma cruzi
title_sort	antiparasitic effect of vitamin b12 on trypanosoma cruzi
url	http://hdl.handle.net/20.500.12110/paper_00664804_v56_n10_p5315_Ciccarelli
work_keys_str_mv	AT ciccarelliab antiparasiticeffectofvitaminb12ontrypanosomacruzi AT frankfm antiparasiticeffectofvitaminb12ontrypanosomacruzi AT puentev antiparasiticeffectofvitaminb12ontrypanosomacruzi AT malchiodiel antiparasiticeffectofvitaminb12ontrypanosomacruzi AT batllea antiparasiticeffectofvitaminb12ontrypanosomacruzi AT lombardome antiparasiticeffectofvitaminb12ontrypanosomacruzi
_version_	1807321918601166848

Antiparasitic effect of vitamin B12 on Trypanosoma cruzi

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