An animal model of iron overload and its application to study hepatic ferritin iron mobilization by chelators.
Administration of 3,5,5-trimethylhexanoyl ferrocene in the diet of male Wistar rats results in a substantial increase in hepatic ferritin protein (greater than 2-fold) and of ferritin iron (4-8-fold). The iron-loading in liver, under the conditions used, appears to be essentially in parenchymal cells rather than in reticulo-endothelial cells. It is suggested that the model represents a useful system for the study of the potential efficacy of new iron chelators for the mobilization of hepatic storage iron. The ability of desferal (DFO) and of a new siderophore, desferrithiocin (DFT), to mobilize hepatic ferritin iron is observed in this model of iron overload. Desferrithiocin stimulates ferritin iron mobilization, when administered either by gavage or by intraperitoneal injection, whereas desferal is active intraperitoneally but inactive orally. Our studies lead to the conclusion that DFT merits further examinations, for its activity as an orally active iron chelator.
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines; D005293:Ferritins / Q000378:metabolism*; D005296:Ferrous Compounds / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D000075163:Metallocenes; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000378:metabolism*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D002614:Chelating Agents; D004095:Dihydropyridines; D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; D011725:Pyridines; D013844:Thiazoles; C050224:3,5,5-trimethylhexanoylferrocene; D005293:Ferritins; D003676:Deferoxamine; C050223:desferrithiocin