Antioxidant effect of Morus nigra on Chagas disease progression.

Considering the widespread popular use of Morus nigra and the amount of scientific information on its antioxidant and anti-inflammatory activity, the effectiveness of this phytotherapeutic compound in the parasitemia progression during the acute phase of Chagas disease and its role in the development of the inflammatory process as well as its effects on the oxidative damage in the chronic phase of infection were evaluated. Thus, 96 male Swiss mice were randomly divided into eight groups, four groups were uninfected controls, and four groups were intraperitoneally infected with 5.0 x 104 blood trypomastigotes forms of T. cruzi QM2 strain. Four batches composed of one uninfected and one infected group were respectively treated with 70% alcohol solution and 25 µL, 50 µL and 75 µL of the phytotherapeutic compound. Levels of antioxidant elements (TBARS, FRAP, GSH and Sulfhydryl groups) were measured in plasma samples. The phytotherapeutic compound's antioxidant activity was measured by polyphenol and total flavonoid quantification, DPPH, NO, and FRAP method. Our results showed that the vehicle influenced some of the results that may have physiological relevance in Chagas disease. However, an important action of M. nigra tincture was observed in the progression of Chagas disease, since our results demonstrated a reduction in parasitemia of treated groups when compared to controls, especially in the group receiving 25 µL. However, in the chronic phase, the 50-µL dosage presented a better activity on some antioxidant defenses and minimized the tissue inflammatory process. Results indicated an important action of M. nigra tincture on the Chagas disease progression.

Evaluation of antioxidant therapy in experimental Chagas disease.

INTRODUCTION:: Stimulation of inflammatory mediators such as cytokines and chemokines may cause oxidative stress in Chagas disease. In this study, we evaluated the merit of vitamins C and E as antioxidant therapy to minimize the oxidative stress-induced damage in an experimental model of Chagas disease. METHODS:: Ninety-six Swiss mice were infected with Trypanosoma cruzi QM2 and treated with vitamins C, E, or both (C/E) for 60 and 120 days, and their effects compared to placebo administration were evaluated in the acute and chronic disease phases. RESULTS:: There was no difference in parasitemia among treatment groups. However, histological analysis showed more severe inflammation in the skeletal muscle in the vitamin supplementation groups at both the acute and chronic phases. Biochemical analyses during the acute phase showed increased ferric-reducing ability of plasma (FRAP) and glutathione (GSH) levels in the vitamin C and C/E groups. In the chronic phase, a decrease in GSH levels was observed in the vitamin E group and a decrease in thiobarbituric acid reactive substances (TBARS) was observed in the vitamin C/E group. Moreover, there was a decrease in TBARS in the cardiac tissues of the vitamin C and C/E groups compared to that of the placebo group, although this level was greater in the vitamin E group than in the vitamin C group. CONCLUSIONS:: The antioxidant action of vitamins C and E reduced oxidative stress in both the acute and chronic phases of Chagas disease, with a marked effect from joint administration, indicating their inherent synergism.

Evaluation of antioxidant therapy in experimental Chagas disease

Abstract INTRODUCTION: Stimulation of inflammatory mediators such as cytokines and chemokines may cause oxidative stress in Chagas disease. In this study, we evaluated the merit of vitamins C and E as antioxidant therapy to minimize the oxidative stress-induced damage in an experimental model of Chagas disease. METHODS: Ninety-six Swiss mice were infected with Trypanosoma cruzi QM2 and treated with vitamins C, E, or both (C/E) for 60 and 120 days, and their effects compared to placebo administration were evaluated in the acute and chronic disease phases. RESULTS: There was no difference in parasitemia among treatment groups. However, histological analysis showed more severe inflammation in the skeletal muscle in the vitamin supplementation groups at both the acute and chronic phases. Biochemical analyses during the acute phase showed increased ferric-reducing ability of plasma (FRAP) and glutathione (GSH) levels in the vitamin C and C/E groups. In the chronic phase, a decrease in GSH levels was observed in the vitamin E group and a decrease in thiobarbituric acid reactive substances (TBARS) was observed in the vitamin C/E group. Moreover, there was a decrease in TBARS in the cardiac tissues of the vitamin C and C/E groups compared to that of the placebo group, although this level was greater in the vitamin E group than in the vitamin C group. CONCLUSIONS: The antioxidant action of vitamins C and E reduced oxidative stress in both the acute and chronic phases of Chagas disease, with a marked effect from joint administration, indicating their inherent synergism.

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

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.

Effects of vitaiin c supplementation on the chronic phase of chagas iisease / Efeitos da suplementação de vitamina C na fase crônica da doença de Chagas

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. .

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. .

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.

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

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.

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.

Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2 strain.

INTRODUCTION: To evaluate the efficacy of vitamin C in reducing the consequences generated by the production of free radicals in the acute and chronic phases of Chagas disease, two different doses of ascorbic acid were administered orally to 60 mice infected by Trypanosoma cruzi QM2 strain. METHODS: The animals were divided into six groups: G1, G2, and G3 for the acute phase study, and G'1, G'2, and G'3 for the chronic stage. The groups G1 and G'1 received 8.6 x 10⁻4 mg/g of vitamin C daily, whereas G2 and G'2 received 7.14 x 10⁻³ mg/g daily. The other groups, G3 and G'3, were considered placebos and received 10 µL of mineral water. RESULTS: The study of the acute phase showed statistically significant differences between G1 and the other groups at various count days of the parasitemia evolution. The multiplying parasite was slower in G1 until the 11th day, but on the 22nd day it had greater parasitemia than in G2 and G3, and from the 36th day on, parasitemia stabilized at higher levels. However, when the histopathology of acute and chronic phases is considered, one does not note significant differences. CONCLUSIONS: The administration of two different doses of vitamin C was not able to protect mice and to contain the oxidative stress caused by free radicals formed by the metabolism of oxygen (reactive oxygen species) and nitrogen (reactive nitrogen species).

Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2 strain / Efeitos da vitamina C em camundongos experimentalmente infectados com a cepa QM2 de Trypanosoma cruzi

INTRODUCTION: To evaluate the efficacy of vitamin C in reducing the consequences generated by the production of free radicals in the acute and chronic phases of Chagas disease, two different doses of ascorbic acid were administered orally to 60 mice infected by Trypanosoma cruzi QM2 strain. METHODS: The animals were divided into six groups: G1, G2, and G3 for the acute phase study, and G'1, G'2, and G'3 for the chronic stage. The groups G1 and G'1 received 8.6x10-4mg/g of vitamin C daily, whereas G2 and G'2 received 7.14x10-3mg/g daily. The other groups, G3 and G'3, were considered placebos and received 10µL of mineral water. RESULTS: The study of the acute phase showed statistically significant differences between G1 and the other groups at various count days of the parasitemia evolution. The multiplying parasite was slower in G1 until the 11th day, but on the 22nd day it had greater parasitemia than in G2 and G3, and from the 36th day on, parasitemia stabilized at higher levels. However, when the histopathology of acute and chronic phases is considered, one does not note significant differences. CONCLUSIONS: The administration of two different doses of vitamin C was not able to protect mice and to contain the oxidative stress caused by free radicals formed by the metabolism of oxygen (reactive oxygen species) and nitrogen (reactive nitrogen species).

INTRODUÇÃO: Para avaliar a eficácia da vitamina C em reduzir as consequências geradas pela produção de readicais livres na fase aguda e crônica da doença de Chagas, duas diferentes dosagens de ácido ascórbico foram administradas oralmente para 60 camundongos infectados pela cepa QM2 de Trypanosoma cruzi. MÉTODOS: Estes animais foram divididos em seis grupos: G1, G2 e G3 para o estudo da fase aguda e G'1, G'2 e G'3 para o estudo da fase crônica. Diariamente, G1-G'1 recebeu 8.6 x 10-4 mg/g de vitamina C, G2- G'2 recebeu 7.14 x 10-3 mg/g. Os outros grupos, G3-G'3, foram considerados placebos e receberam 10µL of de água mineral. RESULTADOS: O estudo da fase aguda mostrou diferenças estatisticamente significativas entre G1 e os outros grupos em vários dias de contagens na evolução da parasitemia, e até o 11º dia a multiplicação parasitária foi menor em G1, mas no 22º dia ele tinha parasitemia maior que G2 e G3, e a partir do 36º, a parasitemia estabilizou em altos níveis. Quando considerado o histopatológico da fase aguda e crônica, não foi notado, entretanto, diferença significativa. CONCLUSÕES: Assim, foi encontrado que a administração de duas diferentes dosagens de vitamina C não foi capaz de proteger o camundongo e conter o estresse oxidativo causado pelos radicais livres formados pelo metabolismo do oxigênio (ROS) e nitrogênio (RNS).

Histogênese da doença renal policística autossômica dominante: estudo imuno-histoquímico / Histogenesis of the cysts in the autosomal dominant polycystic kidney disease. Immunohistochemistry study

A histogênese dos cistos na doença policística autossômica dominante (DRPAD) foi investigada em 33 pacientes por imuno-histoquímica. A idade média dos pacientes foi 46,4 anos e a relaçäo masculino:feminino foi 16:17. A maioria dos pacientes apresentou hipertensäo arterial (88 por cento), insuficiência renal crônica (92 por cento) e hematúria (70 por cento). Aneurismas cerebrais, diverticulose colônica e cistos hepáticos e pancreáticos foram encontrados em 56 por cento dos casos. O peso médio dos 53 rins estudados foi 1468 g e o diâmetro médio dos cistos foi 4,2 cm. Em 4 casos, material histológico de 1 dos rins näo esteve disponível. Os anticorpos e lectinas utilizados para identificar os diferentes segmentos dos néfrons foram: vimentina (Vim)-epitélio parietal da cápsula glomerular (G); Lotus tetragonolubus (LTA) e anti-antígeno CD 15 (Cd 15)-túbulo proximal (TP); anti-proteína de Tamm-Horsfall (PTH)-túbulo distal (TD), e anti-antígeno epitelial de membrana (EMA), anti-citoceratina (Ck) 19, Ulex europaeus (UEA-I), Arachis hypogaea (PNA), Dolichos biflorus (DBA) e Glycine maximum (SBA)-túbulo distal (TD) e ducto coletor (DC). Em estudo piloto, analisaram-se 3 rins normais obtidos de autópsias (rins controles-RC) e áreas preservadas de 2 rins com DRPAD (áreas de controle interno-CI), obtendos-e em todos os casos coloraçäo de: G por Vim, TP-LTA e CD15; TD-PTH; TD e DC-EMA, Ck 19, UEA-I, PNA e DBA. Näo houve coloraçäo com SBA. Os 49 rins com DRPAD produziram o seguinte perfil imuno-histoquímico: i) áreas preservadas: anti-Vim-G=82 por cento; LTA-TP=96 por cento; anti-CD 15-anti-Ck 19-TD e Dc=86 por cento e 89 por cento dos casos, respectivamente; ii) Áreas císticas: LTA, anti-CD 15, anti-PTH, anti EMA e anti-Ck 19=7 por cento, 6 por cento, 18 por cento, 97 por cento e 95 por cento dos casos, respectivamente. Näo houve coloraçäo com anti-Vim. Os resultados indicaram que os cistos em casos de DRPAD têm perfil imuno-histoquímico de túbulos distais e ductos coletores.