Effects of vitamin C supplementation on acute phase Chagas disease in experimentally infected mice with Trypanosoma cruzi QM1 strain

The tissue changes that occur in Chagas disease are related to the degree of oxidative stress and antioxidant capacity of affected tissue. Studies with vitamin C supplementation did not develop oxidative damage caused by Chagas disease in the host, but other studies cite the use of peroxiredoxins ascorbate - dependent on T. cruzi to offer protection against immune reaction. Based on these propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and treated with two different vitamin C doses in order to study the parasitemia evolution, histopathological changes and lipid peroxidation biomarkers during the acute phase of Chagas disease. The results showed that the parasite clearance was greater in animals fed with vitamin C overdose. There were no significant differences regarding the biomarkers of lipid peroxidation and inflammatory process or the increase of myocardium in animals treated with the recommended dosage. The largest amount of parasite growth towards the end of the acute phase suggests the benefit of high doses of vitamin C for trypomastigotes. The supplementation doesn't influence the production of free radicals or the number of amastigote nests in the acute phase of Chagas disease.As alterações teciduais que ocorrem na doença de Chagas estão relacionadas ao grau de estresse oxidativo e à capacidade antioxidante do tecido afetado. Estudos realizados com suplementação de vitamina C revelaram redução no dano oxidativo causado no hospedeiro pela doença de Chagas, porém outros estudos citam o uso de peroxiredoxinas dependentes de ascorbato pelo T. cruzi para se proteger da ação imune. Com base nessas proposições, trinta camundongos "Swiss" foram infectados com a cepa QM1 de T. cruzi e tratados com duas diferentes doses de vitamina C para estudar a evolução da parasitemia, alterações histopatológicas e dosagem de biomarcadores de peroxidação lipídica durante a fase aguda da doença de Chagas. Os resultados mostraram que a parasitemia foi maior nos animais que receberam uma superdosagem de vitamina C. Não houve diferenças significativas quanto aos biomarcadores de peroxidação lipídica e houve maior processo inflamatório no miocárdio dos animais tratados com dosagem recomendada. O maior crescimento parasitário ao fim da fase aguda sugere benefício de altas doses de vitamina C aos tripomastigotas. A suplementação não exerceu influência sobre a produção de radicais livres e o número de ninhos de amastigotas na fase aguda da doença de Chagas

Incidence of Trypanosoma cruzi transmission through breastfeeding during acute experimental Chagas disease

OBJECTIVE: To verify the incidence of T. cruzi transmission through breastfeeding during acute experimental Chagas' disease. METHODS: Fifteen female Swiss mice were mated and, after pregnancy confirmation, placed in individual cages. A few hours after birth, the females were inoculated with 0.1 mL of blood containing approximately 3 x 10(5) trypomastigote forms of Y strain of T. cruzi and continued breastfeeding for 25 days. RESULTS: In 142 offspring examined no infection through breast-feeding was observed. CONCLUSIONS: The low number of trypomastigote forms ingested by the newborn mice combined with biological and biochemical characteristics of blood trypomastigotes may explain the lack of transmission in this experiment

EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE

Introdução: Para verificar a eficácia da vitamina C em combater o insulto oxidativo causado pelo Trypanosoma cruzi durante a evolução da fase crônica da doença de Chagas, camundongos Swiss foram previamente infectados via intraperitoneal com 5.0 × 104 tripomastigotas da cepa QM1 de T. cruzi. Métodos: Camundongos foram suplementados com duas diferentes doses de vitamina C por 180 dias. Foram mensurados os níveis de peroxidação lipídica (indicado por substâncias reativas ao ácido tiobarbitúrico-TBARS), peróxido total, vitamina C, e glutationa reduzida no plasma e TBARS, peróxido total e vitamina C no miocárdio, e foi realizado o estudo histopatológico em coração, cólon e músculo esquelético. Resultados: Animais que receberam diariamente uma dosagem equivalente a 500 mg de vitamina C apresentaram aumento na produção de ROS e RNS no plasma e no miocárdio e maior grau de inflamação e necrose em músculo esquelético em comparação àqueles que receberam doses menores ou nenhuma vitamina C. Conclusão: Embora muitas pesquisas tenham mostrado o efeito antioxidante da vitamina C, nossos resultados mostraram que os animais que foram expostos a 500 mg de vitamina C apresentaram maior dano tecidual na fase crônica da doença de Chagas, provavelmente devido a ações paradoxais desta substância, onde nesta patologia, poderá agir como pró-oxidante ou pró-inflamatória.Introduction: In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain. Methods: Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle. Results: Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever. Conclusion: Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory

Efeitos da suplementação de vitamina C sobre a fase aguda da doença de Chagas em camundongos experimentalmente infectados pela cepa QM1 de Trypanosoma cruzi

The tissue changes that occur in Chagas disease are related to the degree of oxidative stress and antioxidant capacity of affected tissue. Studies with vitamin C supplementation did not develop oxidative damage caused by Chagas disease in the host, but other studies cite the use of peroxiredoxins ascorbate - dependent on T. cruzi to offer protection against immune reaction. Based on these propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and treated with two different vitamin C doses in order to study the parasitemia evolution, histopathological changes and lipid peroxidation biomarkers during the acute phase of Chagas disease. The results showed that the parasite clearance was greater in animals fed with vitamin C overdose. There were no significant differences regarding the biomarkers of lipid peroxidation and inflammatory process or the increase of myocardium in animals treated with the recommended dosage. The largest amount of parasite growth towards the end of the acute phase suggests the benefit of high doses of vitamin C for trypomastigotes. The supplementation doesn't influence the production of free radicals or the number of amastigote nests in the acute phase of Chagas disease

The enigmatic role of cholinergic reflex in the pathogenesis of Chagas disease

This study evaluated the inflammatory process in the colons of mice infected with Trypanosoma cruzi QM2 strain, through the analysis of muscle reactivity and the measurement of butyrylcholinesterase (BuChE) in plasma. Swiss mice were infected with T. cruzi QM2 strain and after 15 (G15), 30 (G30), 60 (G60), 90 (G90), and 210 (G210) days, each group had blood collected for the measurement of butyrylcholinesterase plasma concentrations ([BuChE]), a measure which functioned as an indicator of plasmatic Ach levels. All groups, except G15, had a segment of proximal colon removed to assess muscle reactivity to acetylcholine (Ach) and noradrenaline (NA) stimulation. After reactivity tests, the tissues were then fixed and stained with hematoxylin and eosin (HE) for histological evaluation of inflammatory response. The QM2 strain did induce inflammatory process in mice colon, and demonstrated differences in muscular contraction between the G60 and G210 groups, with p < 0.05. Plasma [BuChE] increased during the acute phase of infection (p < 0.05) with subsequent heterogeneous decline in the late chronic phase. These results show that the QM2 strain has tropism to the colon of mice and causes damage characteristic of megacolon; also, Ach has an enigmatic importance in the anti-inflammatory reflex over the course of T. cruzi infection.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP