Phosphorus protects cardiac tissue by modifying the immune response in rats infected by Trypanosoma cruzi.

AIM: This study evaluates and correlates the number of myocarditis focuses and production of cytokines in Rattus norvegicus (Wistar lineage), experimentally infected with T. Cruzi and treated with Phosphorus. METHODS: In two blind, controlled and randomized trials, 53 45-day-old, male animals were allocated into groups Control (n=24): Control group infected and treated with 7% hydroalcoholic solution, the preparation vehicle of the test medication; and Phosphorus (n=24 on days 0, 5, 10 and 24 after infection): group infected and treated with Phosphorus 13cH, diluted 10-26 and dynamized (test medication). The animals were inoculated intraperitoneally with 5×106 blood trypomastigotes of T. cruzi-Y strain. The medication was administered overnight (16 consecutive hours), diluted in water (1mL/100mL) in amber water bottles. The animals were treated 2days before and 2, 4, and 6days after infection. Enumeration of inflammatory foci in cardiac tissue (Hematoxylin-Eosin) and dosage of cytokines TNF-α and IFN-γ in the serum were performed on days 0, 5, 10 and 24 after infection, using three animals/group. Mann-Whitney, Friedman ANOVA, Spearman correlation (p<0.05), and Statistica Single User Software version 13.2 were used for data analysis. RESULTS: The animals treated with Phosphorus 13cH had high concentration of INF-É£ on the 5th day of infection with significant decrease on the 10th and 24th days (p<0.05), and high concentration of TNF-α on the 5th and 10th days of infection with decrease on the 24th day (p<0.05). The treatment with Phosphorus caused a significant increase of INF-É£ and TNF-α on the 5th day of infection compared with the Control (p<0.05), with reestablishment on the 24th day, as well as in the Control group. The group treated with Phosphorus had 52.5% less number of myocarditis focuses in heart than Control group (p<0.05) on the 10th day of infection. The significant increase in cytokines on the5th day of infection in the Phosphorus group is related to a significant decrease in the number of inflammatory foci in cardiac tissue on the 10th day of infection in this group. DISCUSSION AND CONCLUSION: Treatment with Phosphorus 13cH promotes beneficial effects in T. cruzi infection in Wistar rats by modulating the secretion of IFN-γ and TNF-α with decreased inflammation in cardiac tissue. These results reinforce the importance of considering the use of homeopathy for establishing new therapeutic approaches in the management of patients with Chagas disease.

Increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with Trypanosoma cruzi and treated with highly diluted Lycopodium clavatum.

Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease.

Highly diluted medication reduces tissue parasitism and inflammation in mice infected by Trypanosoma cruzi.

AIM: To evaluate the effects of Kalium causticum, Conium maculatum, and Lycopodium clavatum 13cH in mice infected by Trypanosoma cruzi. MATERIALS AND METHODS: In a blind, controlled, randomized study, 102 male Swiss mice, 8 weeks old, were inoculated with 1400 trypomastigotes of the Y strain of T. cruzi and distributed into the following groups: CI (treated with 7% hydroalcoholic solution), Ca (treated with Kalium causticum 13cH), Co (treated with Conium maculatum 13cH), and Ly (treated with Lycopodium clavatum 13cH). The treatments were performed 48 h before and 48, 96, and 144 h after infection. The medication was repertorized and prepared in 13cH, according to Brazilian Homeopathic Pharmacopoeia. The following parameters were evaluated: infectivity, prepatent period, parasitemia peak, total parasitemia, tissue tropism, inflammatory infiltrate, and survival. Statistical analysis was conduced considering 5% of significance. RESULTS: The prepatent period was greater in the Ly group than in the CI group (p = 0.02). The number of trypomastigotes on the 8th day after infection was lower in the Ca group than in the CI group (p < 0.05). Total parasitemia was significantly lower in the Ca, Co, and Ly groups than in the CI group. On the 12th day after infection, the Ca, Co, and Ly groups had fewer nests and amastigotes/nest in the heart than the CI group (p < 0.05). Decreases in the number of nests and amastigotes in the intestine were observed in the Ly group compared with the CI group (p < 0.05). In the liver (day 12), Ly significantly prevented the formation of inflammatory foci compared with the other groups. In skeletal muscle, Co and Ly decreased the formation of inflammatory foci compared with CI (p < 0.05). Ly afforded greater animal survival compared with CI, Ca, and Co (p < 0.05). The animals in the Co group died prematurely compared with the CI group (p = 0.03). CONCLUSIONS: Ly with 13cH potency had significantly more benefits in the treatment of mice infected with T. cruzi, reducing the number of blood parasites, amastigote nests in tissue, and the number of amastigotes per nest and increasing animal survival.

Maior frequência de administração de bioterápico T. cruzi 17DH diminui parasitemia e aumenta sobrevida de camundongos infectados pelo Trypanosoma cruzi / Higher frequency of administration of biotherapic T. cruzi 17DH decreases parasitemia and increases survival in mice infected with Trypanosoma cruzi

The study of the effect of different ways of treatment using highly diluted substances is rare in the literature. Some authors consider the dose irrelevant, justifying that the action of the medication highly diluted is qualitative [1-3]. Others emphasize the importance of quantity and frequency of administration of the highly diluted substance for a successful treatment [4,5]. The model of murine infection by T. cruzi is widely studied and it is an excellent tool to study the effect of highly diluted substances.There is a difference in the effect of the medication highly diluted depending on the way of treatment used. For mice, the use of drug diluted in water offered frequently, results in better benefits. The clinical use of these results in humans, should consider the allometric system medication dosage which takes into account the metabolic rate of each organism.(AU)

Influência da idade e esquema de tratamento na parasitemia de camundongos infectados pelo Trypanosoma cruzi tratados com bioterápico de alta potência / Influence of age and ways of treatment in the parasitemia in mice infected with Trypanosoma cruzi treated with high potency biotherapy

ABSTRACTIntroduction: The infection of mice by Trypanosoma cruzi is well known, making this a good model for understanding the effect of highly diluted medications. Mice of different ages show different responses to biotherapic T. cruzi [1]. Other data from our laboratory using biotherapic treatment at low potencies show that long lasting treatment has a better effect in mice infected with T. cruzi. However, the use of high potency biotherapics in mice of different ages infected with T. cruzi has not been analysed yet.Conclusion: The age and the ways of treatment used are important factors to be considered when using a highly diluted medication. The clinical use of these results in humans, should take into consideration the allometric system of medication dosage which takes into account the metabolic rate of each organism.(AU)

Introdução: A infecção murina pelo Trypanosoma cruzi é bem conhecida, fazendo deste um bom modelo para o entendimento do efeito de medicamentos ultradiluídos. Camundongos de diferentes idades mostram diferentes respostas a bioterápico de T. cruzi [1]. Outros dados do nosso laboratório utilizando tratamento com bioterápico em baixas potências mostram que o tratamento prolongado exerce melhor efeito em camundongos infectados pelo T. cruzi. No entanto, a utilização de bioterápicos em alta potência em camundongos de diferentes idades infectados pelo T. cruzi ainda não foi explorada.Conclusão: A idade e o esquema de tratamento utilizado são fatores importantes a serem considerados na utilização de medicamento ultradiluído. A utilização clínica destes resultados em humanos, deve considerar o sistema alométrico de dosagem de medicamentos que leva em conta a taxa metabólica de cada organismo.(AU)