A comparative evaluation of iron clearance models.
A comparative study of the non-iron-overloaded, bile duct-cannulated rat and of the Cebus monkey as iron-clearance models is presented. The ability of desferrioxamine, desferrithiocin, and a pyridoxal isonicotinoyl hydrazone (PIH) analogue to clear the metal from these two animals is evaluated. Data suggest that although rodents represent a viable first-line animal screen, there is no strict correspondence between the effectiveness of a chelator in rodents and that in primates. Rodent data should be interpreted carefully as it relates to potential human trials. Iron-loading response, the similarity between multiple human and Cebus serum and hematological values, and the ability to easily observe changes in behavioral patterns clearly render the Cebus monkey the best preclinical screen.
Bergeron
R J
RJ
Department of Medicinal Chemistry, Medicine University of Florida, Gainesville 32610.
Streiff
R R
RR
Wiegand
J
J
Vinson
J R
JR
Luchetta
G
G
Evans
K M
KM
Peter
H
H
Jenny
H B
HB
D000818:Animals; D001646:Bile / Q000737:chemistry; D002614:Chelating Agents / Q000494:pharmacology* / Q000633:toxicity; D003676:Deferoxamine / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D000882:Haplorhini; D006834:Hydrazines / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013054:Spectrophotometry, Atomic; D013844:Thiazoles / Q000494:pharmacology*
D002614:Chelating Agents; D004095:Dihydropyridines; D006834:Hydrazines; D007502:Iron Chelating Agents; D013844:Thiazoles; C065491:CGP 43902A; D007501:Iron; D003676:Deferoxamine; C050223:desferrithiocin