EXCRETION OF COPPER IN COPPER-OVERLOADED FISCHER AND LONG-EVANS CINNAMON RATS TREATED WITH TETRATHIOMOLYBDATE

The mode of excretion of Cu from the liver was studied in Long-Evans C innamon (LEG) rats with an inherently abnormal Cu metabolism and in Cu -loaded Fischer rats by using tetrathiomolybdate (TTM). LEC rats were fed a semisynthetic diet containing 10 ppm Cu for 40 days. Fischer rat s were fed the same diet containing 10 or 500 ppm Cu for 40 days. TTM was injected subcutaneously into the rats at a dose of 5.0 mg/kg at 24 -h intervals for the last 3 days. The hepatic Cu concentrations were 3 92 and 194 mu g/g in Fischer and LEC rats not treated with TTM, respec tively. However, the hepatic MT concentration was about 10 times highe r in the LEC rats than in the Fischer rats. In Fischer rats, the excre tion of Cu into the bile and serum was increased by TTM, resulting in a reduction of the hepatic Cu concentration (264 mu g/g). In LEC rats, leakage of Cu into the serum, but not biliary excretion of Cu, was ac celerated by TTM injection. The increased serum Cu concentration was 0 .7 mu g/ml in LEC rats compared with 14.4 mu g/ml in Fischer rats. The hepatic Cu concentration was 170 mu g/g in LEC rats treated with TTM. Serum ceruloplasmin activity (as oxidase) in LEC rats was not increas ed by the injection of TTM. Our results suggest that TTM can remove Cu from the liver, via blood and, furthermore, that the Cu metabolism in LEC rats is different from that in Cu-fed rats. (C) 1995 Wiley-Liss, Inc.