Fine-structural alterations in Leishmania tropica within human macrophages exposed to antileishmanial drugs in vitro.
The mechanism of action of antileishmanial compounds is poorly understood. Ultrastructural changes in Leishmania tropica within human macrophages exposed in vitro to Pentostam, pentamidine, amphotericin B, WR 6026, ketoconazole, and Formycin B were examined in these experiments. In Pentostam-treated cultures, some organisms exhibited diminished definition of mitochondrial and other membranes, while other organisms had completely disintegrated. Pentostam-exposed macrophages demonstrated loss of membrane definition in the absence of further alterations; it is therefore hypothesized that impaired macrophage membrane function may contribute towards the effect of this drug against macrophage-contained organisms. Leishmania parasites in pentamidine-treated cultures initially demonstrated swollen kinetoplasts and fragmentation of the kinetoplast DNA core. The initial observed effect of the other four drugs on the parasites was cytoplasmic condensation. These ultrastructural studies suggest that all five non-antimonial drugs may have different mechanisms of action than antimony (Pentostam) against Leishmania.
D000634:Aminoquinolines / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000648:ultrastructure; D005573:Formycins / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000648:ultrastructure; D007654:Ketoconazole / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects / Q000648:ultrastructure*; D008264:Macrophages / Q000469:parasitology* / Q000648:ultrastructure; D009940:Organoids / Q000648:ultrastructure; D010419:Pentamidine / Q000494:pharmacology
D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D005573:Formycins; C034561:formycin B; D010419:Pentamidine; D000666:Amphotericin B; D007654:Ketoconazole; C080436:8-aminoquinoline; D000967:Antimony Sodium Gluconate