Biliary copper excretion capacity in intact animals

Correlation between ATP7B function, hepatic mass, and biliary copper excretion

Michael L. Schilsky, Adil N. Irani, Giridhar R. Gorla, Irene Volenberg, Sanjeev Gupta

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Copper toxicosis can occur in the absence of biliary copper excretion. To demonstrate whether biliary copper excretion capacity is correlated with hepatic mass and ATP7B function, we undertook studies in intact animals. Copper-histidine was injected intrasplenically after baseline bile collection, followed by measurement of copper excretion in Long-Evans Cinnamon (LEC) rats lacking atp7b function and in normal, syngeneic Long-Evans Agouti (LEA) rats. The basal biliary copper excretion was very low in LEC rats compared with LEA rats, 8 ± 4 and 37 ± 18 ng copper/min, respectively; p < 0.05. After addition of copper, copper excretion increased significantly (by two- to five-fold) in LEA rats during the 30 minute study period, whereas LEC rats showed only a slight and transient increase in copper excretion. After one-third and two-thirds partial hepatectomy immediately before copper loading, copper excretion decreased progressively. The studies indicate that biliary copper excretion depends on hepatocyte mass and ATP7B gene function. Analysis of copper excretion with our nonradioactive method will facilitate testing of novel therapies and pathophysiological mechanisms in copper toxicity.

Original languageEnglish (US)
Pages (from-to)210-214
Number of pages5
JournalJournal of Biochemical and Molecular Toxicology
Volume14
Issue number4
StatePublished - 2000

Fingerprint

Copper
Animals
Liver
Rats
Inbred LEC Rats
Long Evans Rats
Hepatobiliary Elimination
Hepatectomy
Bile
Toxicity
Hepatocytes
Genes

Keywords

  • ATP7B
  • Biliary Copper Excretion
  • Copper Metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Biliary copper excretion capacity in intact animals : Correlation between ATP7B function, hepatic mass, and biliary copper excretion. / Schilsky, Michael L.; Irani, Adil N.; Gorla, Giridhar R.; Volenberg, Irene; Gupta, Sanjeev.

In: Journal of Biochemical and Molecular Toxicology, Vol. 14, No. 4, 2000, p. 210-214.

Research output: Contribution to journalArticle

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