Anti-parasitic effect of vitamin B12 on Trypanosoma cruzi

CICCARELLI, ALEJANDRA; FRANK, FERNANDA M.; PUENTE, VANESA; MALCHIODI, EMILIO L.; BATTLE, ALCIRA; LOMBARDO, MARIA E.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2012

0066-4804

A nutritional characteristic of trypanosomatid protozoa is that they need a haem-compound as a growth factor. Because of the cytotoxic activity of haem and its structural similarity with cobalamins, we have investigated the effect in vitro and in vivo of vitamin B12 (cyanocobalamin) on the different forms of Trypanosoma cruzi. Cyanocobalamin showed a marked anti-parasitic action against epimastigote  (IC50 2.42 µM), amastigote (IC50 10.69 µM) and trypomastigote (IC50 9.46 µM). Epimastigote and trypomastigote values were 2.5 to 3 times lower than those obtained with benznidazole (reference drug). B12 and hemin do not interact each other in their mode of action. Our results show that B12 increases intracellular oxidative activity and generates superoxide anion, which stimulates both superoxide dismutase (50%) and ascorbate peroxidase (20%) activities. In addition, we found that the antioxidants dithiothreitol or ascorbic acid increase the susceptibility of the parasite to the cytotoxic action of B12. 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 these results, B12 may be considered a potential candidate for novel therapeutic modalities for the treatment of Chagas´ disease.