Trypanosoma cruzi reinfections provoke synergistic effect and cardiac β-adrenergic receptors’ dysfunction in the acute phase of experimental Chagas’ disease

Bustamante, Juan M.; Rivarola, Héctor Walter; Fernández, Alicia Ruth; Enders, Jürgen; Fretes, Ricardo; Gloria, De Luca d’ Oro; Palma, J. A.; Paglini-Oliva, Patrícia

doi:10.1016/s0014-4894(03)00096-1

Cited by 25 publications

(20 citation statements)

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“…However, SGO-Z12-infected mice showed greater compensatory mechanisms, with higher density (p<0.05), allowing us to conclude that cardiac function was less compromised in this group. Similar results were observed in the indeterminate phase of the experimental Chagas' disease (Bustamante et al 2003). Chronic Chagas' disease has a variable course ranging from symptom less infection to severe chronic cardiac disease and even sudden death.…”

Section: Discussionsupporting

confidence: 82%

“…The experiments were carried out on 170 albino Swiss inbred female mice, weighing 30±1 g inoculated with 50 blood trypomastigotes of T. cruzi, strain Tulahuen (Tul-infected group, n=80) or with 50 blood trypomastigotes of T. cruzi, SGO-Z12 isolate (SGO-Z12-infected group n=90), respectively, by intraperitoneal injection as previously described (Bustamante et al 2003). Reinfections were made in 90 of the infected animals, 10 and 20 days after the first inoculation with the parasites, obtaining the following groups: Tul-reinfected group (mice infected and reinfected with 50 bloodstream forms, Tulahuen strain; n=40) and SGO-Z12-reinfected group (mice infected and reinfected with 50 bloodstream forms of T. cruzi, SGO-Z12 isolate; n= 50).…”

Section: Methodsmentioning

confidence: 99%

“…The density and affinity of β-receptors was performed in microsomal fraction of right and left ventricles from noninfected, infected and reinfected mice 135 d.p.i. 3 H/ dihydroalprenolol ( 3 H/DHA, specific activity 3.515 × 10 15 Bq/mol from NEN Life Science Products) was used as radioligand in β-adrenergic receptors' binding assays as described previously (Bustamante et al 2003). Specific binding was defined as the difference in radioactivity bound in the absence or presence of 1 μM propranolol.…”

Section: Methodsmentioning

confidence: 99%

“…People living in endemic areas are exposed to suffer reinfections, a relevant factor even in congenital disease (Rabinovich et al 1990;Catalá et al 2004;Torrico et al 2006). We have previously demonstrated that reinfections with different T. cruzi strains have a potent role in developing early cardiac damage in the acute and indeterminate phase of experimental Chagas' disease (Bustamante et al 2002(Bustamante et al , 2003. These data are in accordance with those who suggest that the parasite by itself, during the acute phase of infection, determines the prognosis of Chagas' disease (Dávila et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Reinfections and Trypanosoma cruzi strains can determine the prognosis of the chronic chagasic cardiopathy in mice

et al. 2007

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Chronic Chagas' disease represents the result of the interaction between the host and the parasite, producing different clinical features: from a mild disease to a severe heart failure. In the present investigation, we analyzed whether Trypanosoma cruzi strain and/or reinfections in the acute stage, determine changes in the chronic phase (135 days postinfection, d.p.i) that could explain the diverse evolution of cardiac lesions. After infection of albino Swiss mice (n = 170) with 50 blood trypomastigote of the T. cruzi, strain Tulahuen (n = 80) and the isolate SGO-Z12 (n = 90), respectively, and reinfections at 10 and 20 d.p.i. Parasitemia, survival, electrocardiography, affinity and density of cardiac beta-receptors and histopathology of the heart were studied. Parasitemias in reinfected mice were significantly higher than those in single-infected mice. Survival of SGO-Z12-infected group was significantly higher than the other groups (p < 0.01). All Tulahuen-reinfected mice and 55-67% of the infected and SGO-Z12-reinfected groups presented some electrocardiographic abnormality (p < 0.01). Hearts from single-infected mice presented fibber disorganization and necrosis; reinfected groups also exhibited fibber fragmentation and a diminished affinity and a higher beta-adrenergic receptors' density than the other groups (p < 0.05). Therefore, parasite strain and reinfections determine different cardiac damage, and either (or both) of these factors are involved in the severity of the clinical picture and the prognosis of the chronic cardiac disease.

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Section: Discussionsupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reinfections and Trypanosoma cruzi strains can determine the prognosis of the chronic chagasic cardiopathy in mice

et al. 2007

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“…In our laboratory, we demonstrated that allopurinol and clomipramine used for the treatment of acute Trypanosoma cruzi infection in mice prevented it from evolving into chronic chagasic cardiopathy (Rivarola et al 2001). Taking into account the high toxicity of the drugs commonly used for Chagas disease treatment, the possible existence of resistant parasite strains, and the coexistence of more than one strain in the same patient, it is possible that the simultaneous administration of two or more drugs with different mechanisms of action, different specificities against parasite strains and different targets, and with fewer adverse side effects could optimize the treatment (Viveiros and Amaral 2001;Bustamante et al 2003;Urbina and Docampo 2003). The aim of the present work was to evaluate the effect of the association of clomipramine and allopurinol for the treatment of experimental Chagas disease in the acute stage.…”

Section: Introductionmentioning

confidence: 99%

Association of clomipramine and allopurinol for the treatment of the experimental infection with Trypanosoma cruzi

et al. 2010

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We have previously shown that clomipramine and allopurinol used separately are effective in preventing chronic chagasic cardiomyopathy. The aim of the present study was to evaluate the effect of the association of clomipramine (Clo--5 mg/kg/day/90 days) and allopurinol (Allo--5, 10, or 15 mg/kg/day/90 days) for the treatment of experimental Chagas disease in the acute stage. Treatment effectiveness was evaluated through parasitemia, survival, electrocardiography, serology, and cardiac histopathology. Groups treated showed no electrocardiographic abnormalities, in contrast to those untreated which presented 25% of mice with conduction alterations. The myocardium of treated mice (Clo, Allo10+Clo, and Allo15+Clo) presented no structural alterations. Cardiac b-receptor affinity was preserved in mice treated with Clo or Clo+Allo at the different doses; receptor density of the Clo and Allo15+Clo groups did not differ from the non-infected group. Anti-cruzipain antibody levels were similar in treated and untreated groups. Survival was significantly increased in the treated groups (p < 0.05), with Clo and all the Clo+Allo groups presenting the highest rates. These results show that the association of clomipramine + allopurinol is effective for Chagas disease treatment and has the same effect as clomipramine alone.

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Chemotherapy of chronic indeterminate Chagas disease: a novel approach to treatment

et al. 2008

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Treatment of Chagas disease is a controversial issue because the available drugs are highly toxic. Clomipramine is a tricyclic antidepressant drug that inhibits Trypanosoma cruzi's trypanothione reductase, provoking the death of the parasite and preventing the cardiac damage when used for the treatment of acutely infected mice. Here, we studied the effectiveness of clomipramine (5 mg/kg/day for one month) as chemotherapy for T. cruzi-infected mice in the chronic indeterminate stage of the infection. The animals were analyzed in the cardiac chronic phase. Survival of treated animals was 84% while for the untreated ones was 40%; most of the animals presented electrocardiographic abnormalities. Affinity and density of cardiac beta receptors from infected and treated mice were similar to those in the indeterminate phase, showing that clomipramine treatment stopped the increment of functional alterations provoked by the infection, while untreated mice presented affinity and density significantly diminished. Hearts from infected and untreated mice in the chronic stage presented mononuclear cells, necrosis and fiber dissolution while hearts from treated animals showed only isolated inflammatory infiltrates. Present results demonstrate that clomipramine used in the chronic indeterminate phase of the T. cruzi infection modified the natural evolution of the chagasic cardiopathy.

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Trypanosoma cruzi reinfections provoke synergistic effect and cardiac β-adrenergic receptors’ dysfunction in the acute phase of experimental Chagas’ disease

Cited by 25 publications

References 25 publications

Reinfections and Trypanosoma cruzi strains can determine the prognosis of the chronic chagasic cardiopathy in mice

Reinfections and Trypanosoma cruzi strains can determine the prognosis of the chronic chagasic cardiopathy in mice

Association of clomipramine and allopurinol for the treatment of the experimental infection with Trypanosoma cruzi

Chemotherapy of chronic indeterminate Chagas disease: a novel approach to treatment

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