Ultrastructural Study of the Effects of Chloroquine and Verapamil on Plasmodium Falciparum

Gretta H. JacobsInstitute of Pathology, Case Western Reserve University, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Cleveland, Ohio 44106

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Ayo M. J. Oduola
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Dennis E. Kyle
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Wilbur K. Milhous
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Samuel K. Martin
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Masamichi AikawaInstitute of Pathology, Case Western Reserve University, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Cleveland, Ohio 44106

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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 × 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 × 10-4 M) of verapamil alone.

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