Reversibility of hepatic mitochondrial damage in rats with long-term cholestasis.

Details

Serval ID
serval:BIB_E1F23C6ECD7E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Reversibility of hepatic mitochondrial damage in rats with long-term cholestasis.
Journal
Journal of hepatology
Author(s)
Krähenbühl L., Schäfer M., Krähenbühl S.
ISSN
0168-8278 (Print)
ISSN-L
0168-8278
Publication state
Published
Issued date
06/1998
Peer-reviewed
Oui
Volume
28
Number
6
Pages
1000-1007
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Long-term bile duct ligation in rats is associated with secondary biliary cirrhosis and metabolic alterations, e.g. mitochondrial dysfunction. We performed the current studies to characterize the reversibility of hepatic mitochondrial dysfunction after reversing biliary obstruction by Roux-en-Y anastomosis.
Rats were studied after 4 weeks of bile duct ligation, and after 5 or 14 days of reanastomosis. Control rats were pair-fed to treated rats and all rats were studied after starvation for 24 h. Mitochondria were isolated by differential centrifugation and enzyme activities determined by spectrophotometric methods.
In comparison to controls, plasma beta-hydroxybutyrate concentrations were decreased in bile duct ligated rats (200+/-70 vs. 790+/-200 micromol/l) and remained decreased after relief of biliary obstruction. In contrast, plasma free fatty acids were not different between controls and treated rats. Oxidative metabolism of L-glutamate, succinate and duroquinol was decreased in liver mitochondria from bile duct ligated rats. After relief of biliary obstruction, the metabolism of L-glutamate and duroquinol normalized quickly, whereas succinate metabolism remained impaired. Similar results were obtained for the mitochondrial oxidases in disrupted mitochondria. The activities of complex I, II, III and V of the respiratory chain were reduced in bile duct ligated rats. After relief of biliary obstruction, complex I and III normalized quickly, whereas complex II and V remained impaired. Oxidative metabolism of long-chain fatty acids by isolated liver mitochondria was decreased in bile duct ligated rats and did not recover after relief of biliary obstruction.
Long-term cholestasis in the rat is associated with a decrease in specific functions of liver mitochondria which recover only partially after Roux-en-Y anastomosis. The persistence of decreased mitochondrial fatty acid metabolism cannot be explained by impaired activity of the respiratory chain, but is more likely due to alterations in mitochondrial beta-oxidation.
Keywords
3-Hydroxybutyric Acid, Adenosine Triphosphatases/metabolism, Anastomosis, Roux-en-Y, Animals, Bile Ducts/physiology, Bile Ducts/surgery, Carrier Proteins, Cholestasis/blood, Cholestasis/metabolism, Electron Transport Complex II, Electron Transport Complex III/metabolism, Fatty Acids, Nonesterified/blood, Food Deprivation, Glutamic Acid/metabolism, Hydroquinones/metabolism, Hydroxybutyrates/blood, Male, Membrane Proteins/metabolism, Mitochondria, Liver/metabolism, Multienzyme Complexes/metabolism, NAD(P)H Dehydrogenase (Quinone)/metabolism, Oxidative Phosphorylation, Oxidoreductases/metabolism, Oxygen Consumption, Rats, Rats, Sprague-Dawley, Succinate Dehydrogenase/metabolism, Succinates/metabolism
Pubmed
Web of science
Create date
11/12/2018 12:41
Last modification date
20/08/2019 17:06
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