Strain-related patterns of biliary excretion and hepatic distribution of copper in the rat

Abstract

Biliary copper excretion was studied in male, bile-cannulated rats of the inbred strains Fischer, Brown Norway, WAG/Rij and Lewis. After intravenous injection of 10, 30 and 50 micrograms copper per 100 gm body weight, two patterns of copper excretion were observed; their profiles varied with the copper dose and the strain of the rats used. The lowest amounts of copper were excreted by Fischer rats, the highest by WAG/Rij rats; this was related to the effect of the copper dose on both patterns. The subcellular distribution of copper in the liver was studied in Fischer and Brown Norway rats after doses of 50, 100, and 200 micrograms per 100 gm body weight. Brown Norway rats accumulated more copper in the liver, although the copper concentration was the same in both strains 1 hr after injection of all doses. Fischer rats accumulated proportionally more copper in lysosomal and nuclear mitochondrial fractions whereas Brown Norway rats accumulated proportionally more copper in the cytosol. Gel filtration of liver supernatants revealed that the amount of copper accumulating in the protein presumed to be metallothionein was 2 to 3 times higher in Brown Norway rats, whereas in the Fischer rats more copper eluted in the void volume fraction. We conclude that both biliary copper excretion and copper distribution in the liver are under genetic control. Because of its low copper excretion and reduced binding of copper to metallothionein the Fischer rat, compared to other strains, may be a suitable model for studying the involvement of the liver in copper intoxication.

Effect of chronic exposure to excess dietary copper and dietary selenium supplementation on liver specimens from rats

“…33 Additionally, although different rat strains have variable susceptibility to Cu toxicosis, the Fischer 344 strain was reported to be a susceptible strain. 34 It is important to emphasize the vast differences in handling excess Cu between mammalian species. Diets containing Cu concentrations less than that used in our study have been reported to cause liver injury in other species.…”

Biliary copper excretion capacity in intact animals: Correlation between ATP7B function, hepatic mass, and biliary copper excretion

“…The capacity for biliary copper excretion has been incompletely defined, although it is known that copper excretion into bile increases after systemic copper administration [4,8,9]. Removal of copper requires hepatocellular copper uptake, intracellular processing, and excretion via the bile canaliculus.…”