Differential effect of amphotericin B on the three evolutive stages of Trypanosoma cruzi and on the host cell-parasite interaction.
1. Amphotericin B (Am.B) was shown to have a direct effect on T. cruzi, with the three forms of the parasite presenting different susceptibilities to the drug in the following order: amastigotes > trypomastigotes > epimastigotes. These differences highlight the importance of using the vertebrate forms of the parasite in tests of new drugs. 2. The treated parasites showed alterations of the plasma membrane, suggesting that, as in fungi, the primary effect of Am.B was probably via formation of complexes with membrane components. 3. When exposed to filipin, another polyene antibiotic, the three parasite forms were observed to present a similar order of susceptibility, with comparable ultrastructural modifications. 4. Higher concentrations of Am.B were required to damage the intracellular parasites in vitro, 2.3 micrograms/ml for parasites inside peritoneal macrophages and 7 micrograms/ml for parasites inside heart muscle cells. 5. Am.B is effective against the parasite, but is also toxic to mammalian cells. Testing of Am.B for the control of Chagas' disease by blood transfusion may be useful, since bloodstream forms are lysed by lower concentrations of the drug than those required to affect intracellular parasites.
de-Castro
S L
SL
Departamento de Ultraestrutura e Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
Soeiro
M N
MN
Higashi
K O
KO
Meirelles
M N
MN
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D001803:Blood Transfusion; D014355:Chagas Disease / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005372:Filipin / Q000494:pharmacology; D006790:Host-Parasite Interactions / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000666:Amphotericin B; D005372:Filipin