Effect of colchicine on the clearance of ferritin in vivo.
The effect of the microtubular inhibitor colchicine, administered at either 0.036 (dose 1) or 5 mumol/kg (dose 2), on hepatic ferritin uptake was determined over a 5-h period of ferritin infusion in normal and iron-loaded rats. In the absence of colchicine, the serum ferritin concentration of normal rats was reduced after 5 h to 20 +/- 9% and in iron-loaded rats to 30 +/- 1% of the expected values, indicating ferritin clearance. After colchicine (dose 1), a similar result was observed in normal rats; however, in iron-loaded rats, an increase in serum ferritin to 77 +/- 16% of the expected value indicated a decreased ferritin clearance and/or increased ferritin release. The administration of the higher dose to normal rats also resulted in an increase in serum ferritin to 72 +/- 2% of the expected value. In iron-loaded rats, after dose 2 the ferritin concentration rose to 359 +/- 108% of the expected value, consistent with the release of endogenous ferritin. Colchicine administration had no effect on biliary ferritin in normal rats; however, in iron-loaded rats, both doses resulted in a fivefold increase in the release of biliary ferritin. The results suggest that ferritin uptake is facilitated by receptor-mediated endocytosis, which is partially inhibited by colchicine. Release of ferritin also occurs as a result of colchicine administration, and this is dependent on both the dose of colchicine and the iron status of the animal.
Ramm
G A
GA
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Australia.
Powell
L W
LW
Halliday
J W
JW
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology*; D005293:Ferritins / Q000097:blood / Q000378:metabolism*; D007505:Iron-Dextran Complex / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007505:Iron-Dextran Complex; D005293:Ferritins; D003078:Colchicine