Treatment with benznidazole or thioridazine in the chronic phase of experimental Chagas disease improves cardiopathy.
Mice infected with Trypanosoma cruzi Tulahuen strain or SGO-Z12 isolate were treated at 180 days post infection (p.i.) (i.e. chronic phase) with benznidazole (for 30 days) or thioridazine (for 12 days). Both drugs produced a decrease in electrocardiographic alterations, fewer modifications in the affinity and density of cardiac beta-receptors, and few isolated areas of fibrosis in the heart, whereas untreated mice presented areas of necrosis and fibre fragmentation 350 days p.i. (P<0.01). Survival in treated mice was 100% for benznidazole and 88% for thioridazine, independent of the parasite strain; survival for untreated mice was 30% and 40% for Tulahuen strain and SGO-Z12 isolate, respectively (P<0.01). No cardiotoxic effects of thioridazine were detected at the dose and treatment schedule used. These results show the benefit of treatment in the chronic phase of Chagas disease and that thioridazine should be considered as a promising agent for the treatment of Chagas disease.
Bustamante
Juan M
JM
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5000 Córdoba, Argentina. juanbus@uga.edu
Presti
María S Lo
MS
Rivarola
Héctor W
HW
Fernández
Alicia R
AR
Enders
Julio E
JE
Fretes
Ricardo E
RE
Paglini-Oliva
Patricia
P
D000818:Animals; D002598:Chagas Cardiomyopathy / Q000188:drug therapy*; D014355:Chagas Disease / Q000188:drug therapy*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013881:Thioridazine / Q000494:pharmacology / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use*
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D013881:Thioridazine; C009999:benzonidazole