Thiotungstate-copper interactions II. The effects of tetrathiotungstate on systemic copper metabolism in normal and copper-treated rats.
The intraperitoneal administration of tetrathiotungstate to rats (6-17.4 mg W/Kg BW) caused profound changes in copper metabolism in both normal rats and in rats pretreated with copper. Plasma copper associated with albumin increased, liver copper, particularly cytosol copper, was depleted, and biliary excretion was increased. There was also a movement of copper to higher molecular weight proteins in both liver cytosol and bile. In contrast to penicillamine, tetrathiotungstate did not increase liver cytosolic apometallothionein levels and reduced the rise provoked by copper. Metallothionein-bound copper was removed. Ceruloplasmin oxidase activity was inhibited and there was evidence for increased movement of copper into subcellular organelles, probably lysosomes. It is concluded that tetrathiotungstate has a genuine "decoppering" effect and could be considered as an alternative to thiomolybdates in the treatment of copper storage diseases.
McQuaid
A
A
Biochemistry Department, Trinity College, Dublin University, Ireland.
Lamand
M
M
Mason
J
J
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D010396:Penicillamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D017973:Tungsten Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
D017973:Tungsten Compounds; D003300:Copper; D008668:Metallothionein; D002570:Ceruloplasmin; D010396:Penicillamine; D015032:Zinc