Document Detail

Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats.
MedLine Citation:
PMID:  12242607     Owner:  NLM     Status:  MEDLINE    
In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu(6)-Cp) or totally Cu-unoccupied Cu(0)-Cp (apo-Cp), but not partially Cu-occupied Cu(n)-Cp (where n = 1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats.
Yutaka Komatsu; Yasumitsu Ogra; Kazuo T Suzuki
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Publication Detail:
Type:  Journal Article     Date:  2002-06-25
Journal Detail:
Title:  Archives of toxicology     Volume:  76     ISSN:  0340-5761     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-20     Completed Date:  2003-04-16     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  502-8     Citation Subset:  IM    
Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522, Japan.
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MeSH Terms
Apoproteins / metabolism
Ceruloplasmin / metabolism*
Chromatography, High Pressure Liquid
Copper / metabolism*
Glutathione / metabolism
Hepatitis, Chronic / metabolism*
Hepatolenticular Degeneration / metabolism*
Indicators and Reagents
Indocyanine Green
Liver / metabolism
Liver Function Tests
Rats, Inbred LEC
Rats, Wistar
Reg. No./Substance:
0/Apoproteins; 0/Indicators and Reagents; 0/apoceruloplasmin; 3599-32-4/Indocyanine Green; 70-18-8/Glutathione; 7440-50-8/Copper; EC

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