Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas' heart disease

Budni, Patrícia; Pedrosa, Roberto Coury; Farias, Mirelle Sifroni; Parisotto, Eduardo Benedetti; Dalmarco, Eduardo Monguilhott; Frode, Tânia Sílvia; Oliveira‐Silva, Diogo; Colepicolo, Pio; Filho, Danilo Wilhelm

doi:10.1016/j.ijcard.2009.06.033

Cited by 39 publications

(34 citation statements)

References 48 publications

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“…Employing a low concentration of B 12 (0.25 M), both antioxidants enhanced considerably the antiparasitic activity in vitro. As expected (9,17), the antioxidants showed a dose-dependent antiparasitic activity, reaching 8-fold inhibition when DTT and ascorbic acid were used at 1.0 and 1.5 M, respectively (Table 2).…”

Section: Resultssupporting

confidence: 74%

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Ciccarelli

Frank

Puente

et al. 2012

Antimicrob Agents Chemother

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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.

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Section: Resultssupporting

confidence: 74%

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Ciccarelli

Frank

Puente

et al. 2012

Antimicrob Agents Chemother

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“…After the antioxidant intervention essentially all these OS biomarkers were normalized to control levels [3] (see details below). Thus the antioxidant intervention was able to confer a protective effect against the oxidative insult associated with airborne contamination derived from emissions of an electric power plant, in a way very similar to the results obtained in other projects carried out by our research group involving other chronic diseases, such as chronic cardiopathy associated with Chaga's disease [32] and also patients with chronic hepatitis C [33], using the same protocol for antioxidant intervention.…”

Section: '5''s; 48supporting

confidence: 80%

“…In contrast, the studies from our laboratory indicate that the antioxidant therapy with vitamins E and C during six months was effective in significantly attenuating the systemic blood oxidative insult associated with exposure to coal extraction and combustion, as well as to SRHS incineration, and that such nutritional intervention might be recommended for subjects exposed to these airborne contaminations. This antioxidant efficacy was already demonstrated in other diseases [56], as well by our research group in patients with chronic cardiopathy associated with Chagas' disease [32] and with hepatitis C [33], using the same protocol of antioxidant intervention. In this regard, among other aspects involving the experimental design and protocols used in related studies that may explain, at least in part, doses above 400 IU of vitamin E are necessary to counteract elevated systemic OS in humans [55].…”

Section: Discussionsupporting

confidence: 68%

Systemic Oxidative Stress Promoted by Emissions of Particulate Matter is Attenuated by Antioxidant Supplementation

Possamai¹,

Avila²,

Filho³

2015

eee

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Emissions of different types of airborne particulate matter (PM) is associated either with occupational contamination that affect both, workers directly exposed to the distinct PM sources such as incineration of solid residues of health services, coal mining and also coal burning derived from an electric-power plant, as well as the population living in the vicinity of such emissions. Such contamination leads to endogenous overgeneration of reactive oxygen species (ROS) in different cells and tissues and therefore to a systemic oxidative stress (OS). Enzymatic and non-enzymatic OS biomarkers were measured in the blood of workers directly and indirectly (near the emissions) exposed and also in subjects indirectly exposed living in the vicinities of these PM emissions, before and after a six months antioxidant intervention of a daily oral supplementation of vitamins C (500 mg) and E (400 mg). Compared to baseline values, the antioxidant intervention after 6 months was able to confer a consistent and protective effect against the systemic OS irrespective of the PM source of the airborne contaminants. The results clearly indicate that supplementation with antioxidant vitamins could be recommended in order to attenuate the deleterious consequences of a systemic OS associated with such PM emissions.

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“…Although our group has never treated chagasic patients with benznidazole combined with cyanocobalamin and ascorbic acid, Ribeiro et al 8 have conducted a study where they administered vitamins C and E for 6 months following the termination of benznidazole treatment. The authors concluded that supplementation with both vitamins reduced the oxidative stress produced by the disease itself, as well as that produced by the administration of benznidazole.…”

Section: Dear Editormentioning

confidence: 98%

“…In this way, vitamin C might either reduce or enhance the oxidative burst when simultaneously administered with benznidazole, and therefore concerns exist regarding this treatment's effi cacy and safety. On the other hand, the evidence provided by studies conducted in chronic chagasic patients may justify the use of vitamin C following termination of benznidazole treatment, in order to decrease the oxidative stress 8 .…”

Section: Dear Editormentioning

confidence: 99%

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

Andrade

Oliveira

Nagão-Dias

et al. 2014

Rev. Soc. Bras. Med. Trop.

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Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas' heart disease

Cited by 39 publications

References 48 publications

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Systemic Oxidative Stress Promoted by Emissions of Particulate Matter is Attenuated by Antioxidant Supplementation

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

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Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas' heart disease

Cited by 39 publications

References 48 publications

Antiparasitic Effect of Vitamin B 12 on Trypanosoma cruzi

Antiparasitic Effect of Vitamin B 12 on Trypanosoma cruzi

Systemic Oxidative Stress Promoted by Emissions of Particulate Matter is Attenuated by Antioxidant Supplementation

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

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Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi