Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine onTrypanosoma cruzi |
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| Authors: | J L Lacuara S R de Barioglio P P de Oliva A S Bernacchi A F de Culasso J A Castro B M Franke de Cazzulo J J Cazzulo |
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| Affiliation: | (1) Instituto de Fisiologia, Facultad de Ciencias Medicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5009 Córdoba;(2) Centro de Investigaciones Toxicológicas, CITEFA/CONICET, Zufriategui 4380, 1603 Villa Martelli, Buenos Aires;(3) Instituto de Investigaciones Bioquímicas Fundación Campomar, A. Machado 151, 1405 Buenos Aires, (Argentina) |
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| Abstract: | Summary The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes ofTrypanosoma cruzi, at concentrations lower than 100  M, and motility and infectivity of the bloodstream trypomastigote form at 200 M. 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 M 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. |
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| Keywords: | Trypanosoma cruzi trifluoperazine mitochondrial ATPase trypanocidal drugs |
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