Chemotherapy of chronic indeterminate Chagas disease: a novel approach to treatment.
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.
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, PC 5000, Córdoba, Argentina.
Paola Carolina
PC
Bazán
María Silvina
MS
Lo Presti
Héctor Walter
HW
Rivarola
María Fernanda
MF
Triquell
Ricardo
R
Fretes
Alicia Ruth
AR
Fernández
Julio
J
Enders
Patricia
P
Paglini-Oliva
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy* / Q000503:physiopathology; D002997:Clomipramine / Q000627:therapeutic use*; D004562:Electrocardiography; D006321:Heart / Q000503:physiopathology; D051379:Mice; D009206:Myocardium / Q000473:pathology; D011941:Receptors, Adrenergic / Q000502:physiology; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000981:Antiprotozoal Agents; D011941:Receptors, Adrenergic; D002997:Clomipramine