Effect of drugs on Trypanosoma cruzi and on its interaction with heart muscle cell "in vitro".
Megazol, nifurtimox, benznidazol and allopurinol were investigated, by light and electron microscopy, for their action on T. cruzi. Both the direct effect upon amastigote and trypomastigote forms and the effect upon the interaction of heart muscle cells (HMC) with bloodstream trypomastigotes were studied. The proliferation of amastigotes in Warren medium was inhibited in a dose-dependent manner by megazol, nifurtimox and benznidazol. Treatment of amastigotes (25-50 microM/24 h) and trypomastigotes (25 microM/24h) led to several ultrastructural alterations in the parasites. These three drugs also had a potent effect on the treatment of infected heart muscle cells when added at the beginning of the interaction or after one or three days of infection. The interiorized parasites showed a similar pattern of ultrastructural alterations as observed by the direct effect on the amastigotes. The primary heart muscle cell culture proved to be a suitable model for the study of drugs on intracellular parasites. Likewise, the amastigote proliferation in axenic medium was shown to be an adequate assay for an initial trial of drugs. These parameters seem very reliable to us for a systematic investigation of the mechanism of action of new drugs.
de Castro
S L
SL
Instituto Oswaldo Cruz, Departamento de Ultraestrutura e Biologia Celular, Rio de Janeiro, Brasil.
de Meirelles
M de N
Mde N
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000469:parasitology*; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D009547:Nifurtimox / Q000494:pharmacology*; D009581:Nitrofurans / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D013830:Thiadiazoles / Q000494:pharmacology*; D014344:Trypanocidal Agents; D014349:Trypanosoma cruzi / Q000187:drug effects*
D009581:Nitrofurans; D009593:Nitroimidazoles; D013830:Thiadiazoles; D014344:Trypanocidal Agents; D000493:Allopurinol; D009547:Nifurtimox; C009999:benzonidazole