Molybdenum and copper kinetics after tetrathiomolybdate injection in LEC rats: specific role of serum albumin.
Chelation therapy with tetrathiomolybdate (TTM) was applied to Long-Evans rats with a cinnamon coat-color (LEC rats), an animal model for Wilson disease, to remove copper (Cu) accumulated in the liver in a form bound to metallothionein (MT). Changes in molybdenum (Mo) and Cu concentrations and their biological forms in serum of LEC rats determined at different times after a single intraperitoneal injection were compared with those of Wistar (normal) rats. The change in Mo concentration in serum of normal rats was mono-phasic, whereas in LEC rats it was bi-phasic. The phase in normal rats and the first phase in LEC rats appeared to reflect the process of uptake and disappearance of TTM in the livers of Wistar and LEC rats. On the other hand, the second phase in LEC rats paralleled the changes of Cu and appeared to reflect the complex formation (Cu/thiomolybdate complex) between Mo and Cu accumulated in the liver. The complex was specifically bound to albumin as determined by high performance liquid chromatography with inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). The results suggested that the changes in the Mo concentration in serum reflected the amount of Cu in the liver.
Suzuki
K T
KT
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Ogra
Y
Y
Ohmichi
M
M
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000652:urine; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008982:Molybdenum / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D011485:Protein Binding; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects
D002614:Chelating Agents; D012709:Serum Albumin; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate