Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/5711
Title: Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy.
Authors: Andrade, Sonia Gumes
Guerret, Sylviane Stocker
Pimentel, Ariane R
Grimaud, Jean Alexis
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Institut Pasteur de Lyon. Centro de Microscopie Eletronique. Lyon, France
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Institut Pasteur de Lyon. Centro de Microscopie Eletronique. Lyon, France
Abstract: This investigation was performed to verify the effect of specific chemotherapy (Benznidazole or MK-436) on the inflammatory and fibrotic cardiac alterations in mice chronically infected with the strains 21 SF (Type II) and Colombian (Type III) of Trypanosoma cruzi. To obtain chronically infected mice, two groups of 100 Swiss mice each, were infected with either the 21 SF or the Colombian strain (2 x 10(4) and 5 x 10(4) blood forms respectively). The rate of mortality in the acute phase was of 80% for both groups. Twenty surviving mice chronically infected with the 21 SF strain and 20 with the Colombian strain were then divided in treated and untreated groups. Excluding those that died during the course of treatment, 14 mice chronically infected with the 21 SF strain and 15 with the Colombian strain were finally evaluated in the present study. Chemotherapy was performed with Benznidazole (N-benzil-2-nitro-1-imidazolacetamide) in the dose of 100 mg/k.b.w/day, for 60 days, or with the MK-436 (3(1-methyl-5 nitroimidazol-2-yl) in two daily doses of 250 mg/k.b.w, for 20 days. Parasitological cure tests were performed (xenodiagnosis, haemoculture, subinoculation of the blood into newborn mice), and serological indirect immunofluorescence test. The treated and untreated mice as well as intact controls were killed at different periods after treatment and the heart were submitted to histopathological study with hematoxilineosin and picrosirius staining; ultrastructural study; collagen immunotyping, fibronectin and laminin identification by immunofluorescence tests. Results: the untreated controls either infected with 21 SF or Colombian strain, showed inflammatory and fibrotic alterations that were mild to moderate with the 21 SF strain and intense with the Colombian strain. Redpicrosirius staining showed bundles of collagen in the interstitial space and around cardiac fibers. Increased deposits of matritial components and collagen fibers, macrophages and fibroblasts appeared at the ultrastructural examination. Deposits of fibronectin, laminin, pro-III and IV collagens were seen, most intense in those infected with the Colombian strain. Treated mice, parasitologically cured, presented clear-cut regression of the inflammatory lesions and of the interstitial matrix thickening. Mice infected with the Colombian strain and treated with MK-436, was parasitologically cured in 5/6 cases and showed mild inflammatory infiltration and fibrosis. The mice treated with Benznidazole (Colombian strain) did not cure and showed moderate fibrosis and inflammation. Treatment of the mice infected with the 21 SF with Benznidazole determined parasitological cure of all animals, that showed mild inflammation and fibrosis of the myocardium
Keywords: Trypanosoma cruzi
Chronic myocarditis
Collagen immunotyping
Fibronectin
Laminin
Chemotherapy
DeCS: Cardiomiopatia Chagásica/quimioterapia
Nitroimidazóis/uso terapêutico
Animais
Cardiomiopatia Chagásica/parasitologia
Cardiomiopatia Chagásica/patologia
Modelos Animais de Doenças
Fibrose Endomiocárdica/quimioterapia
Fibrose Endomiocárdica/parasitologia
Fibrose Endomiocárdica/patologia
Matriz Extracelular/ultraestrutura
Camundongos
Miocárdio/ultraestrutura
Especificidade da Espécie
Issue Date: 1991
Citation: ANDRADE, S.G. et al. Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy. Memórias do Instituto Oswaldo Cruz, v. 86, n. 2, p. 187-200, apr.-jun. 1991.
ISSN: 0074-0276
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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