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Vol. 282, Issue 1, 108-112, 1997

Heme Polymerase Activity and the Stage Specificity of Antimalarial Action of Chloroquine

Augustine U. Orjih

MLS Department, Faculty of Allied Health Sciences, Kuwait University, Sulaibikhat 90805, Kuwait, Arabian Gulf

Plasmodium falciparum lysate, prepared from 2.7 × 107 ring-infected erythrocytes and incubated with hemoglobin in sodium acetate at pH 5, incorporated a mean of 1.6 nmol of ferriprotoporphyrin IX (FP) into hemozoin in 18 to 22 hr. A similar preparation of trophozoite lysate incorporated a mean of 3.6 nmol of FP into hemozoin in 4 to 6 hr. These findings indicate differences between heme polymerase activity (hemozoin production) at the ring and trophozoite stages of malaria parasites. Intracellular hemozoin production was 90% inhibited at the ring and trophozoite stages by 0.5 and 7 nmol of chloroquine/106 infected erythrocytes. respectively. The inhibition killed the rings but not the trophozoites, suggesting that mature parasites may have a mechanism for protecting themselves against chloroquine-FP toxicity.


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Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.