Biliary copper excretion in acutely and chronically copper-loaded rats

Biliary copper excretion was examined in rats with acute, continuous and chronic copper loads. Copper was excreted into bile, and the concentration peaked 40 min after a venous injection of copper sulfate (127 ng/gm body weight). The excretion was significantly inhibited by colchicine. Therefore some copper may be transported in hepatocytes by a vesicular pathway and excreted into bile. Biliary copper output increased over time and reached a plateau 180 min after a continuous venous infusion of copper sulfate (318 ng/gm body weight/hr) had started, when the concentration of copper in bile was much higher than that in plasma; the bile/plasma ratio of copper concentrations was 4.32 +/- 0.46. These data support the idea that copper transport involves a specific uptake and transport system. In chronically copper-loaded rats, hepatic copper content was significantly increased compared with controls, and reaction products for copper were observed in hepatocyte granules by light microscopic examination with p-dimethylaminobenzylidene rhodanine stain. The number of lysosomes in hepatocytes increased and the shape changed. In chronically copper-loaded rats the number of tubular lysosomes was very high. However, other organelles appeared to be normal. In these rats biliary excretion of not only copper but also acid phosphatase, a lysosomal enzyme, was significantly greater than the control. Therefore hepatocyte lysosomes may play an important role in biliary copper excretion. Furthermore, when biliary lysosomal excretion increases, the tubular lysosomes actively participate in this excretion.