Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice.
Trypanosoma cruzi trypanothione reductase is an enzyme that has been identified as a potential target for chemotherapy. Thioridazine inhibits it and prevented cardiopathy in mice infected with T. cruzi Tulahuen strain. As not all T. cruzi strains respond to treatment in the same way, an isolate from a chronic patient (SGO Z12) was used; parasitaemias were studied along with, survival, serology, electrocardiography, histology and cardiac beta receptor function. Parasitaemia in thioridazine (80 mg/(kg day) for 3 days) treated mice was less and lasted for a shorter period (P < 0.01), there were reduced electrocardiographic and histological alterations and significantly improved survival (80% of non-treated died). Treated mice had lower receptor affinity and higher density as a compensatory mechanism, modifying the course of T. cruzi infection (SGO Z12 isolate) and preventing the consequent cardiopathy.
Lo Presti
M S
MS
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5000 Córdoba, Argentina.
Rivarola
H W
HW
Bustamante
J M
JM
Fernández
A R
AR
Enders
J E
JE
Fretes
R
R
Gea
S
S
Paglini-Oliva
P A
PA
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002598:Chagas Cardiomyopathy / Q000517:prevention & control*; D014355:Chagas Disease / Q000150:complications* / Q000188:drug therapy*; D004195:Disease Models, Animal; D004562:Electrocardiography; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000187:drug effects; D018512:Parasitemia; D016019:Survival Analysis; D013881:Thioridazine / Q000494:pharmacology* / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000913:Antibodies, Protozoan; D014344:Trypanocidal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D013881:Thioridazine