Altera??es inflamat?rias induzidas pelo tratamento com Cloridrato de Amiodarona em modelo experimental da infec??o pelo Trypanosoma cruzi.

Abstract

Programa de P?s-Gradua??o em Ci?ncias Biol?gicas. N?cleo de Pesquisas em Ci?ncias Biol?gicas, Pr?-Reitoria de Pesquisa de P?s Gradua??o, Universidade Federal de Ouro Preto.A doen?a de Chagas se desenvolve ap?s a infec??o pelo protozo?rio Trypanosoma cruzi. Este parasito desencadeia uma resposta imune em seu hospedeiro mam?fero mediado por c?lulas, anticorpos e mediadores inflamat?rios, culminando em destrui??o do tecido e perda funcional do ?rg?o, a exemplificar, o cora??o e o trato gastrointestinal em humanos. F?rmacos com o intuito de amenizar os danos funcionais card?acos t?m sido empregados na cl?nica m?dica e, nos ?ltimos anos, tamb?m identificadas suas a??es sob a resposta imune. Dentre estes f?rmacos, encontra-se o antiarr?tmico Cloridrato de Amiodarona (CA). O objetivo deste estudo ? avaliar a a??o do tratamento com o CA na infec??o aguda pela cepa VL-10 do T. cruzi em modelo murino. Para tal, realizou-se a infec??o de camundongos C57BL/6, agrupados em (i) animais tratados com 30mg/kg de CA diariamente e (ii) animais tratados com PBS 1x + metilcelulose 0,5% (ve?culo). Ap?s 30 dias de tratamento, realizou-se a necr?psia e coleta de soro e ?rg?os (cora??o, f?gado e ba?o) para a dosagem de citocinas e avalia??o do peso relativo dos ?rg?os, respectivamente, al?m de an?lise histol?gica. Observou-se redu??o nos n?veis dos parasitas sangu?neos ao final do tratamento e redu??o dos n?veis plasm?ticos e card?acos de TNF-? e CCL2, mas n?o de CCL5 e IL-10. Al?m disso, observou-se menor aumento do peso relativo do cora??o e ba?o associado ao tratamento com CA. Estes dados sugerem uma a??o parcial do CA sobre T. cruzi e a resposta imune do hospedeiro, principalmente mediada por TNF-? e CCL-2, na infec??o experimental pelo T. cruzi, cepa VL-10, em animais isog?nicos C57BL/6.Chagas disease is a clinical condition developed after Trypanosoma cruzi infection. This parasite triggers an immune response mediated by immune cells, antibodies, and inflammatory mediators from mammalian host resulting in tissue destruction and loss of function in different organs, such as heart and gastrointestinal tract observed in humans. Drugs used to mitigate the functional cardiac damage have been used in clinical medicine and, in recent years, also demonstrated their actions in the modulation of the immune response. Among these drugs the antiarrhythmic amiodarone (AD) is evidenced. The aim of this study is to evaluate the effect of the AD treatment in acute infection with T.cruzi VL-10 strain in murine model. C57BL/6 mice were grouped into (i) animals treated with 30mg/kg daily with AD and (ii) animals treated with water + 5% methylcellulose (vehicle). After 30 days of treatment, we performed a necropsy and serum and organs (heart, liver and spleen) were collected for cytokines and organ weights evaluations, respectively, and also histological analysis. There was a reduction in the levels of blood parasites after the treatment in paralell with a reduction of plasma and cardiac levels of TNF-? and CCL2, but not CCL5 and IL-10. In addition, there was a smaller increase in the relative weight of the heart and spleen associated with treatment with AD. Together, these data suggest a partial action of the AD on the immune response, mainly in TNF-? and CCL-2 production during inbread C57BL/6 mice experimentally infected with VL-10 strain of T. cruzi

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