Biliary copper excretion in the neonatal rat: Role of glutathione and metallothionein

✍ Scribed by Parvathi Mohan; Mark Failla; Ian Bremner; Ann Arthur-Smith; Benny Kerzner

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 790 KB
• Volume: 21
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840210425

✦ Synopsis

Metallothionein (MT) and glutathione (GSH) have been implicated as two major copper-binding agents involved in the hepatobiliary copper metabolism in the adult rat. This study was designed to explore their potential role in facilitating copper export from the copper-laden hepatocyte of the newborn rat. Biliary and hepatic copper, GSH, and immunoreactive 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, and freeze-dried. The bile flow rate (BFR) doubled and the liver weight increased 14-fold during maturation. Hepatic and biliary copper and MT-I concentrations were significantly higher in the suckling than in the weanling. The total biliary output of copper per 24 hours was low at 1 week and increased significantly by 8 weeks of age. MT-I-bound copper represented a maximum of only 3.4% of biliary copper at 1 week and 0.5% at 8 weeks. GSH was not detected in bile until 2 weeks and then increased 15fold by 8 weeks, while hepatic GSH levels remained unchanged. Therefore, GSH levels did not correlate with the high biliary copper concentration at week 1, although there was a close correlation between the total daily biliary excretion of copper and GSH at 2 weeks and beyond. We conclude that the net biliary copper excretion per day is relatively low in the first week of life and is independent of MT and GSH secretion. It increases significantly once GSH is available in bile. We speculate that biliary copper excretion in the neonatal rat may involve copper binding agents as yet unidentified.