Iron chelators: in vitro inhibitory effect on the liver stage of rodent and human malaria.
The activity of desferrioxamine (Desferal) and desferrithiocin (a newly developed oral iron chelator) was evaluated against the liver stage of Plasmodium yoelii and P. falciparum in the rodent and the human hepatocyte in vitro culture system. The two iron chelators were found to inhibit the liver schizogony of both the rodent and the human Plasmodium species at concentrations achievable in vivo. P. falciparum proved to be more sensitive (ic 95% below 20 micromol/l than P. yoelii (ic 95% 50-100 micromol/l). As assessed by electron microscopy, drug administration was associated with focal clarification of the cytoplasm thought to be reversible. As desferrioxamine and desferrithiocin are known to be equally active on the blood stage of rodent and human plasmodia, iron chelators are deserving of further investigation as potential alternative candidates to existing drugs for radical cure of malaria.
D000818:Animals; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000469:parasitology / Q000648:ultrastructure; D008288:Malaria / Q000188:drug therapy; D008854:Microscopy, Electron; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
D004095:Dihydropyridines; D007502:Iron Chelating Agents; D013844:Thiazoles; D003676:Deferoxamine; C050223:desferrithiocin