Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

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 B 12 (or cyanocobalamin) on the different forms of Trypanosoma cruzi. Cyanocobalamin showed a marked antiparasitic activity against epimastigotes (50% inhibitory concentration [IC 50 ], 2.42 M), amastigotes (IC 50 , 10.69 M), and trypomastigotes (IC 50 , 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 B 12 and hemin do not interact with each other in their modes of action. Our results show that B 12 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 B 12 . We propose that vitamin B 12 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 B 12 and Bnz should be further investigated due to its potential as a new therapeutic modality for the treatment of Chagas' disease.

The potential role of vitamins in the management of Chagas disease

“…Another recent study suggests that the combined use of gentian violet, ascorbic acid, and light to sterilize blood infected with Trypanosoma cruzi effectively prevents transfusion-based transmission of Chagas disease 3 . Other similar, recent data suggest that vitamin B12 may be of clinical value in the treatment of Chagas disease; vitamin B12 activity against trypomastigotes and epimastigotes is particularly significant 4 . Vitamin B12 mediates this anti-parasitic role by accentuating superoxide dismutase activity, which leads to augmented intracellular production of reactive oxygen species.…”

Authors' reply: Vitamins in the treatment of chronic Chagas disease: adjuvant antiparasitary or antioxidant therapy?

“…Marim et al 5 have recently reported that vitamin C administration reduced parasitemia, although no effect was observed regarding the number of amastigote nets in the other tissues 6 . This phenomenon might limit the effi cacy of the combined treatment in the chronic phase, as other researchers have reported no statistically signifi cant histopathological differences in chronically infected mice that were treated with vitamin C for 180 days 7 .…”

The role of benznidazole with cyanocobalamin and ascorbic acid in treating the chronic phase of Chagas disease

“…As well, Ciccarelli et al 5 have demonstrated that cyanocobalamin markedly decreased the motility and growth rate of Trypanosoma cruzi epimastigotes, where its cytotoxic action is thought to occur through the generation of ROS. Moreover, ascorbate peroxidase activity is significantly increased by cyanocobalamin, and ascorbic acid is known to intensify the antiparasitic activity of cyanocobalamin.…”

“…This mechanism of action is likely due to the well-known prooxidant effects of these compounds, which, when combined with transition metal ions (Co, Cu, and Fe), generate ROS 6 . Accordingly, in the study of Ciccarelli et al 5 , the antiparasitic effect of Bnz treatment was further enhanced by the coadministration of cyanocobalamin and ascorbic acid. As well, it has previously be reported that the that treatment of blood infected with Trypanosoma cruzi with ascorbic acid, light, and gentian violet effectively prevents transmission of Chagas disease 7 .…”