REMOVAL OF COPPER FROM THE LIVER OF LONG-EVANS CINNAMON (LEC) RATS BYTETRATHIOMOLYBDATE (TTM) INJECTION - THE MAIN EXCRETION ROUTE IS VIA BLOOD, NOT BILE

Tetrathiomolybdate (TTM) was injected at a dose of 10 mg/kg bw daily f or eight consecutive days into Long-Evans Cinnamon (LEC) rats, which i nherently abnormally deposit Cu (260 mu g/g) in the liver. The hepatic Cu (100 mu g/g) and metallothionein (MT) bound Cu (from 2,600 to 540 mu g/g protein) concentrations were decreased greatly by the injection . On the other hand, the renal Cu concentration increased significantl y, but the brain Cu concentration only very slightly. The reduction of the hepatic Cu concentration was accompanied by reductions of Zn and Fe concentrations in the liver, kidney and brain. The TTM compound sli ghtly stimulated excretion (about 3-fold) of Cu into the bile, but gre atly (about 40-fold) into the blood. In rats not treated with TTM, mos t biliary (100%) and serum (78%) Cu was recovered in the trichloroacet ic acid (TCA) soluble fraction. On the other hand, in rats treated wit h TTM, bile and serum Cu were recovered overwhelmingly in the TCA inso luble fraction, probably in the form of a Cu-TTM-albumin complex. Our results suggest that although there is an inherent failure in the intr insic secretory process of Cu from the liver in LEC rats, the TTM comp ound can remove Cu from Cu-MT, resulting in a decrease of hepatic Cu.