Effect of the microtubular inhibitor vinblastine on ferritin clearance and release in the rat.
We have previously demonstrated that colchicine inhibits ferritin clearance from the circulation of normal and iron-loaded rats and stimulates endogenous ferritin release into both the serum and bile of iron-loaded rats. The aim of the present study was to determine the effect of vinblastine on ferritin clearance and release in normal and iron-loaded rats. Vinblastine was administered at either 1 or 10 mg/kg to both normal and iron-loaded rats, infused over a 5 h period with either a rat liver ferritin or saline solution. Serum and biliary ferritin levels were determined every 30 min. After 5 h, 90% of the infused ferritin was cleared from the circulation in the absence of vinblastine. Low-dose vinblastine decreased ferritin uptake 10-20% in iron-loaded rats. High-dose vinblastine inhibited ferritin clearance by 25% in normal rats and 20-40% in iron-loaded rats. Vinblastine administration caused a 2-3-fold increase in the serum ferritin concentration and a 3-5-fold peak in biliary ferritin levels. Thus, vinblastine caused the release of endogenous ferritin into both the serum and bile of iron-loaded rats in the presence of a ferritin load. We therefore conclude that disturbed microtubule function accounts for the observed inhibition of ferritin uptake and intracellular transport; however, the mechanism of increased ferritin release remains unclear.
Ramm
G A
GA
Liver Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
Powell
L W
LW
Halliday
J W
JW
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D005293:Ferritins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007457:Iodine Radioisotopes; D019190:Iron Overload / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D014747:Vinblastine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D007457:Iodine Radioisotopes; D014747:Vinblastine; D005293:Ferritins