Impacto da obesidade em camundongos Balb/c machos infectados com Trypanosoma cruzi e sua relação com aspectos imunológicos e histopatológicos
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Data
2019-02-15
Autores
Arruda, Camila Maria de
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Universidade Estadual Paulista (Unesp)
Resumo
A Doença de Chagas, causada pelo Trypanosoma cruzi (T. cruzi), é uma patologia infecciosa crônica que apresenta grande incidência no Brasil e, nos últimos anos, passou a ser endêmica em centros urbanos. É acompanhada por alterações no sistema imune com variações nos níveis séricos das citocinas pró-inflamatórias. O tratamento disponível no Brasil é o benzonidazol, com baixa eficácia na fase crônica e efeitos colaterais importantes. Sabe-se que os adipocitos são reservatórios de T. cruzi, aspecto importante que é a relação com as citocinas pro-inflamatórias e com o aumento de T.cruzi nos adipocitos interferindo na evolução da doença. Sendo assim, o objetivo do presente estudo foi avaliar os efeitos da obesidade e das citocinas pro inflamatórias em camundongos balb/c machos infectados com T. cruzi tratados ou não com benzonidazol. Foram utilizados 120 animais, divididos em seis grupos, sendo 3 com dieta normal e 3 com dieta hipercalórica. Esses foram avaliados em cinco momentos: M1-1°dia, M2-3°dia, M3-5°dia, M4-7°dia e M5-8°dia. Para infecção utilizou a cepa aguda Y, com pico de parasitemia no sétimo dia (M4). A eutanásia foi realizada em cinco animais de cada grupo, em cada momento. Para determinação das citocinas utilizou o Kits de CBA –Cytometric Beads Array, através de citômetro de fluxo. Além disso, foi verificado o peso da gordura. O medicamento foi ofertado na dosagem de 100 mg/Kg/dia. A análise estatística foi realizada por medidas descritivas com o cálculo de média, desvio padrao, minimo, maximo e mediana, testes ANOVA, Tukey, Wald e Qui-quadrado. Dentre os resultados observa-se que houve aumento do peso relativo e de gordura corporal entre os consumiram dieta hipercalórica, classificando-os com obesidade. Além disso, pode-se verificar que as alterações metabólicas e inflamatórias estão mais elevadas nos grupos obesos, sendo eles infectados ou não, com ou sem tratamento. Portanto o estado nutricional tem uma grande influencia no processo infeccioso pelo T. cruzi. O presente estudo revelou que a obesidade desencadeia alterações inflamatórias detectadas pelas citocinas pro inflamatórias e metabólicas, e que a associação com o processo infeccioso agravou esse processo. O tratamento com benzonidazol contribuiu para uma resposta melhor com menos alterações metabólicas e inflamatórias
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a chronic infectious disease that has a high incidence in Brazil and, in recent years, has become endemic in urban centers. It is accompanied by changes in the immune system with variations in serum levels of pro-inflammatory cytokines. The available treatment in Brazil is benzonidazole, with low efficacy in the chronic phase and important side effects. It is known that the adipocytes are reservoirs of T. cruzi, an important aspect that is the relation with the pro-inflammatory cytokines and with the increase of T. cruzi in the adipocytes interfering in the evolution of the disease. Therefore, the objective of the present study was to evaluate the effects of obesity and proinflammatory cytokines in T. cruzi infected or non-treated male balb / c mice with benzonidazole. A total of 120 animals were used, divided into six groups: 3 with normal diet and 3 with hypercaloric diet. These were evaluated in five moments: M1-1 day, M2-3 day, M3-5 day, M4-7 day and M5-8 day. For infection, the acute Y strain was used, with a peak of parasitemia on the seventh day (M4). Euthanasia was performed in five animals from each group, at each moment. In order to determine the cytokines, the CBA-Cytometric Beads Array Kits were used by flow cytometer. In addition, the fat weight was checked. The drug was offered in the dosage of 100 mg / kg / day. Statistical analysis was performed by descriptive measures with mean, standard deviation, minimum, maximum and median, ANOVA, Tukey, Wald and Chi-square tests. Among the results it was observed that there was an increase in relative weight and body fat among those consuming a hypercaloric diet, classifying them as obese. In addition, it can be verified that the metabolic and inflammatory alterations are higher in the obese groups, being they infected or not, with or without treatment. Therefore, the nutritional status has a great influence on the T. cruzi infectious process. The present study revealed that obesity triggers inflammatory changes detected by pro-inflammatory and metabolic cytokines, and that association with the infectious process aggravated this process. Benzonidazole treatment contributed to a better response with fewer metabolic and inflammatory changes
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a chronic infectious disease that has a high incidence in Brazil and, in recent years, has become endemic in urban centers. It is accompanied by changes in the immune system with variations in serum levels of pro-inflammatory cytokines. The available treatment in Brazil is benzonidazole, with low efficacy in the chronic phase and important side effects. It is known that the adipocytes are reservoirs of T. cruzi, an important aspect that is the relation with the pro-inflammatory cytokines and with the increase of T. cruzi in the adipocytes interfering in the evolution of the disease. Therefore, the objective of the present study was to evaluate the effects of obesity and proinflammatory cytokines in T. cruzi infected or non-treated male balb / c mice with benzonidazole. A total of 120 animals were used, divided into six groups: 3 with normal diet and 3 with hypercaloric diet. These were evaluated in five moments: M1-1 day, M2-3 day, M3-5 day, M4-7 day and M5-8 day. For infection, the acute Y strain was used, with a peak of parasitemia on the seventh day (M4). Euthanasia was performed in five animals from each group, at each moment. In order to determine the cytokines, the CBA-Cytometric Beads Array Kits were used by flow cytometer. In addition, the fat weight was checked. The drug was offered in the dosage of 100 mg / kg / day. Statistical analysis was performed by descriptive measures with mean, standard deviation, minimum, maximum and median, ANOVA, Tukey, Wald and Chi-square tests. Among the results it was observed that there was an increase in relative weight and body fat among those consuming a hypercaloric diet, classifying them as obese. In addition, it can be verified that the metabolic and inflammatory alterations are higher in the obese groups, being they infected or not, with or without treatment. Therefore, the nutritional status has a great influence on the T. cruzi infectious process. The present study revealed that obesity triggers inflammatory changes detected by pro-inflammatory and metabolic cytokines, and that association with the infectious process aggravated this process. Benzonidazole treatment contributed to a better response with fewer metabolic and inflammatory changes
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Palavras-chave
obesidade, Citocina IL6, TNFα, doença de chagas, Obesity, Cytokine IL6, Chagas disease