Ultrastructural study of the effects of chloroquine and verapamil on Plasmodium falciparum.
Verapamil, a calcium antagonist, has recently been shown to reverse chloroquine resistance in malarial parasites in vitro. We report the first ultrastructural morphological changes associated with this phenomenon using chloroquine-sensitive and -resistant clones of Plasmodium falciparum. While the administration of 6.3 x 10(-8) M chloroquine had little morphological effect on the chloroquine-resistant strain, the combination of chloroquine and verapamil resulted in typical chloroquine-related food vacuolar swelling with increased amounts of granular matrix. Secondary morphological changes included degeneration of nuclei, mitochondria, and other organelles. These effects appeared similar to those in the chloroquine-sensitive strain of P. falciparum treated with chloroquine alone or with the chloroquine/verapamil combination. Furthermore mild food vacuolar changes were seen in a small number of parasites (from both chloroquine-sensitive and -resistant groups) exposed to high concentrations (1 x 10(-4) M) of verapamil alone.
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004347:Drug Interactions; D004351:Drug Resistance; D008854:Microscopy, Electron; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure; D014700:Verapamil / Q000494:pharmacology*
D002738:Chloroquine; D014700:Verapamil