Copper metabolism after biliary fistula, obstruction, or sham operation in rats

Intravenously administered carrier-free 67Cu appeared rapidly in the bile of rats with a recently created biliary fistula; maximal excretion occurred within the first 2 hours. However, if the biliary fistula had been created 3 or 4 days before injection of the 67Cu, only one-fourth to one-half as much of the isotope appeared in the bile. There also was a small decrease in stable biliary copper. When rats with biliary fistula were compared with rats with permanent biliary obstruction, over a period of 6 weeks, both exhibited a marked increase in plasma copper and an equally pronounced increase in the rho-phenylenediamine oxidase activity of plasma but no increase in hepatic copper. Peaks in blood were reached within 2 weeks and then slowly diminished. Sham-operated rats had parallel, but much lower, copper and enzyme changes. Correlations between these rat studies and the copper retention of Wilson's disease and of primary biliary cirrhosis are suggested.