Accumulation of orally given cadmium in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism.
An inherent defect of biliary Cu excretion and subsequent Cu deposition in the liver have been found in Long-Evans Cinnamon (LEC) rats, which are promising models of Wilson disease. LEC and Fischer rats were given water containing Cd (CdCl2) at a level of 5 ppm for 30 days. Regardless of drinking Cd water, LEC rats showed a very high concentration of Cu (200 to 250 microgram/g) and Cu-metallothionein (Cu-MT) (18 mg/g) in the liver. There was no difference of Cd accumulation in the liver between the two strains exposed to Cd (2.6 and 2.7 microgram/g in the Fischer and LEC groups, respectively). However, the renal Cd concentration was slightly but significantly higher in LEC rats (3.5 microgram/g) than in Fischer rats (2.0 microgram/g). The ratio of renal Cd contents to the sum of renal and hepatic Cd contents was significantly higher in LEC rats (0.25) than in Fischer rats (0.15). The serum Cd concentration in Cd-treated LEC rats increased threefold compared to Cd-treated Fischer rats. It seems likely that Cd from the liver is transported into the kidney in the form of Cd, Cu-MT. There was no difference in uptake of Cd in the hepatic MT fraction between the two strains. Although biliary Cu excretion in LEC rats was significantly lower than that in Fischer rats, reduced excretion of Cd into bile was not found in LEC rats. The gross amounts of Cu and Cu-MT influenced the accumulation of Cd in the kidney rather than in the liver when Cd was given orally at a low level to LEC rats. Our results suggest tht Cu and Cd do not share the same sites of hepatobiliary excretion in rats, although the main route of their excretion is via bile.
Sugawara
N
N
Department of Public Health, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Lai
Y R
YR
Sugawara
C
C
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D002104:Cadmium / Q000493:pharmacokinetics*; D019256:Cadmium Chloride; D002712:Chlorides / Q000493:pharmacokinetics*; D003300:Copper / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D013045:Species Specificity
D002712:Chlorides; D002104:Cadmium; D003300:Copper; D019256:Cadmium Chloride