Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro.
Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.
Whitehead
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Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, England.
Peto
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D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D007042:Hypoxanthines / Q000378:metabolism; D010963:Plasmodium falciparum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism
D000962:Antimalarials; D007042:Hypoxanthines; D003676:Deferoxamine