Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine on Trypanosoma cruzi.
The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes of Trypanosoma cruzi, at concentrations lower than 100 microM, and motility and infectivity of the bloodstream trypomastigote form at 200 microM. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 microM TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.
Lacuara
J L
JL
Instituto de Fisiologia, Facultad de Ciencias Medicas, Universidad Nacional de Córdoba, Argentina.
de Barioglio
S R
SR
de Oliva
P P
PP
Bernacchi
A S
AS
de Culasso
A F
AF
Castro
J A
JA
Franke de Cazzulo
B M
BM
Cazzulo
J J
JJ
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects; D009840:Oligomycins / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D009840:Oligomycins; D014344:Trypanocidal Agents; D014268:Trifluoperazine; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases