BILIARY COPPER EXCRETION IN THE NEONATAL RAT - ROLE OF GLUTATHIONE AND METALLOTHIONEIN

Metallothionein (MT) and glutathione (GSH) have been implicated as two major copper-binding agents involved in the hepatobiliary copper meta bolism in the adult rat, This study was designed to explore their pote ntial role in facilitating copper export from the copper-laden hepatoc yte of the newborn rat, Biliary and hepatic copper, GSH, and immunorea ctive MT-I concentrations were measured in Sprague-Dawley rats at 1, 2 , 3, 4, and 8 weeks of age, Bile was collected by duct cannulation for 90 minutes before the rats were killed. Liver was removed, weighed, a nd freeze-dried, The bile flow rate (BFR) doubled and the Liver weight increased 14-fold during maturation. Hepatic and biliary copper and M T-I concentrations were significantly higher in the suckling than in t he weanling, The total biliary output of copper per 24 hours was low a t 1 week and increased significantly by 8 weeks of age, MT-I-bound cop per represented a maximum of only 3.4% of biliary copper at I week and 0.5% at 8 weeks. GSH was not detected in bile until 2 weeks and then increased 15-fold by 8 weeks, while hepatic GSH levels remained unchan ged, Therefore, GSH levels did not correlate with the high biliary cop per concentration at week 1, although there was a close correlation be tween the total daily biliary excretion of copper and GSH at 2 weeks a nd beyond. We conclude that the net biliary copper excretion per day i s relatively low in the first week of life and is independent of MI an d GSH secretion. It increases significantly once GSH is available in b ile, We speculate that biliary copper excretion in the neonatal rat ma y involve copper binding agents as yet unidentified.