Heme polymerase activity and the stage specificity of antimalarial action of chloroquine
Orjih, A.U.
Journal of Pharmacology and Experimental Therapeutics 282(1): 108-112
1997
ISSN/ISBN: 0022-3565 PMID: 9223546 Document Number: 479713
Plasmodium falciparum lysate, prepared from 2.7 times 10-7 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/10-6 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.