Association of clomipramine and allopurinol for the treatment of the experimental infection with Trypanosoma cruzi.
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.
Gobbi
Paola
P
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, PC 5000 Córdoba, Argentina.
Baez
Alejandra
A
Lo Presti
Maria Silvina
MS
Fernández
Alicia R
AR
Enders
Julio E
JE
Fretes
Ricardo
R
Gea
Susana
S
Paglini-Oliva
Patricia A
PA
Rivarola
Hector Walter
HW
D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D014355:Chagas Disease / Q000188:drug therapy*; D002997:Clomipramine / Q000008:administration & dosage*; D003546:Cysteine Endopeptidases / Q000276:immunology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000188:drug therapy; D015800:Protozoan Proteins; D016019:Survival Analysis; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000302:isolation & purification
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D000493:Allopurinol; D003546:Cysteine Endopeptidases; C063214:cruzipain; D002997:Clomipramine