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Iron Chelators: In Vitro Inhibitory Effect on the Liver Stage of Rodent and Human Malaria

Erich Stahel^*, Dominique Mazier^*, Andre Guillouzo, Francois Miltgen, Irene Landau, Sylvie Mellouk^*, Richard L. Beaudoin, Patrik Langlois^¶ AND Marc Gentilini^*

^* Department de Parasitologie et de Médecine Tropicale, INSERM U 313, Groupe Hospitalier Pitié-Salpetrière, 75013 Paris, France
INSERM U 49, Hôpital Pontchaillou, 35000 Rennes, France
Museum National d'Histoire Naturelle, Laboratoire de Zoologie-Vers, 75005 Paris, France
Naval Medical Research Institute, Bethesda, Maryland 20814
^¶ Service de Chirurgie, Groupe Hospitalier Pitié-Salpetrière, 75013 Paris, France

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.

Accepted for publication March 1, 1988.

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