Excretion of copper complexed with thiomolybdate into the bile and blood in LEC rats.
Copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease, was removed with ammonium tetrathiomolybdate (TTM), and the fate of the Cu complexed with TTM and mobilized from the liver was determined. TTM was injected intravenously as a single dose of 2, 10 or 50 mg TTM/kg body weight into LEC and Wistar (normal Cu metabolism) rats, and then the concentrations of Cu and molybdenum (Mo) in the bile and plasma were monitored with time after the injection. In Wistar rats, most of the Mo was excreted into the urine, only a small quantity being excreted into the bile, while Cu excreted into the urine decreased. However, in LEC rats, Cu and Mo were excreted into the bile and blood, and the bile is recognized for the first time as the major route of excretion. The Cu excreted into both the bile and plasma was accompanied by an equimolar amount of Mo. The relative ratio of the amounts of Cu excreted into the bile and plasma was 40/60 for the low and high dose groups, and 70/30 for the medium dose group. The systemic dispositions of the Cu mobilized from the liver and the Mo complexed with the Cu were also determined for the kidneys, spleen and brain together with their urinal excretion. Although Mo in the three organs and Cu in the kidneys and spleen were increased or showed a tendency to increase, Cu in the brain was not increased at all doses of TTM.
Komatsu
Y
Y
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Sadakata
I
I
Ogra
Y
Y
Suzuki
K T
KT
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D008982:Molybdenum / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D020332:Rats, Inbred LEC; D017208:Rats, Wistar
D002614:Chelating Agents; D003300:Copper; D008982:Molybdenum; D008668:Metallothionein; C020809:tetrathiomolybdate