THE EFFECT OF CHLOROQUINE AND RELATED ANTIMALARIALS ON HAEM IN Plasmodium falciparum

摘要

The malaria parasite, Plasmodium falciparum is responsible for the most virulent form of malaria and predominates in Africa affecting children and pregnant women most severely. The parasite feeds by ingesting red blood cell cytosol composed essentially of haemoglobin. The globin component is digested while the haem moiety is released and auto-oxidised to toxic ferrihaem. Ferrihaem is detoxified in part by conversion to insoluble, chemically inert haemozoin (malaria pigment). Haemozoin is chemically and structurally identical to a synthetic ferrihaem called β-haematin. Studies have shown that chloroquine and related antimalarials are able to inhibit the formation of β-haematin in vitro via the formation of a ferrihaem-drug complex. It has therefore been suggested that chloroquine and related drugs are haemozoin inhibitors, acting by preventing the incorporation of ferrihaem into haemozoin in vivo by forming a ferrihaem-drug complex. In our investigation, cultures of Plasmodium falciparum were inoculated with various concentrations of chloroquine and incubated for a period of 32 hours. The amounts of haemoglobin, haem, haemozoin (measured as a Fe(III)haem complex) and total iron present in these cultures were determined using a combination of spectroscopic assays.