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Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Abstract

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed.

Trypanosoma cruzi; phenothiazines; calcium antagonists; parasite-host cell interactions


ABSTRACT

Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Solange L. de Castro1

Maria Nazaré C. Soeiro1

Maria de Nazareth Leal de Meirelles1

Instituto Oswaldo Cruz, Departamento de Ultraestrutura e Biologia Celular, Rio de Janeiro, Brasil

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed.

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Publication Dates

  • Publication in this collection
    04 June 2009
  • Date of issue
    June 1992
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