Effects of antimalarials and protease inhibitors on plasmodial hemozoin production

Wanida Asawamabasakda, Isra Ittarat, Chih Ching Chang, Peter McElroy, Steven R. Meshnick

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Malarial hemozoin may play an important role as a target for antimalarial drugs and in disease pathogenesis. A new assay for hemozoin was developed in which the hemozoin was separated from cells by filtration. Trophozoites have substantially more hemozoin than rings, but there are relatively small differences between chloroquine-sensitive and chloroquine-resistant strains. The effects on hemozoin content of chloroquine and artemisinin, two antimalarial drugs, and E64 and Pepstatin A, two protease inhibitors, were measured. At concentrations at which hypoxanthine incorporation was unaffected, the hemozoin content of rings was decreased by E64, but not by the other three compounds. Artemisinin and Pepstatin A also had little effect on the hemozoin content of trophozoites. Chloroquine and E64 inhibited trophozoite hemozoin formation, but inhibited hypoxanthine uptake to a similar or greater extent. When either rings or trophozoites were exposed to several higher concentrations of chloroquine, hemozoin content was diminished, but significantly less than hypoxanthine uptake. Various concentrations of E64, in contrast, inhibited hemozoin production by both rings and trophozoites significantly more than hypoxanthine incorporation, suggesting that hemozoin production may be directly affected by E64.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume67
Issue number2
DOIs
Publication statusPublished - 1994 Oct

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Molecular Biology

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