Antiparasitic Effect of Vitamin B12on Trypanosoma cruzi

Abstract

ABSTRACTA 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 thein vitroandin vivoeffect of vitamin B12(or cyanocobalamin) on the different forms ofTrypanosoma 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 B12and hemin do not interact with each other in their modes of action. Our results show that B12increases 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 B12exerts its growth-inhibitory effect through the generation of reactive oxygen species. In anin vivoassay, a significant reduction in the number of circulating parasites was found inT. 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 B12and Bnz should be further investigated due to its potential as a new therapeutic modality for the treatment of Chagas' disease.