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Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease
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  1. P Ljubuncic,
  2. Z Tanne,
  3. A Bomzon
  1. Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  1. Dr A Bomzon, Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, PO Box 9649, Haifa, Israel 31096. bomzon{at}tx.technion.ac.il

Abstract

BACKGROUND There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individuals with chronic liver disease and animal models of liver disease. Hence, by virtue of their increased presence in the circulation, it is not unreasonable to suppose that they may account for extrahepatic tissue damage in chronic liver disease.

MATERIALS AND METHODS This hypothesis was tested by determining plasma levels of the ubiquitous antioxidant glutathione (GSH) and lipid peroxides (LP), together with assessment of the extent of lipid peroxidation in the kidney, brain, and heart, in 24 day chronically bile duct ligated (CBDL) rats. The extent of lipid peroxidation in tissues was based on measurement of conjugated dienes, lipid peroxides, and malondialdehyde (MDA) content. Data were compared with identical data collected from unoperated control, pair fed, 24 day bile duct manipulated (sham operated), and pair fed sham operated rats.

RESULTS In CBDL rats, total and reduced plasma GSH levels were almost half those determined in all control rats. Plasma, kidney, and heart LP levels were significantly increased in CBDL rats compared with controls. MDA levels were significantly higher in the kidney, brain, and heart homogenates prepared from CBDL rats compared with MDA content measured in tissue homogenates prepared from the four groups of control rats.

CONCLUSIONS Our data show that experimental cholestatic liver disease is associated with increased lipid peroxidation in the kidney, brain, and heart. Hence we have concluded that the oxidative stress in cholestatic liver disease is a systemic phenomenon probably encompassing all tissues and organs, even those separated by the blood-brain barrier.

  • cirrhosis
  • oxidative stress
  • lipid peroxidation
  • lipid peroxides
  • conjugated dienes
  • malondialdehyde
  • glutathione
  • Abbreviations used in this paper

    BDL/CBDL
    (chronic) bile duct ligated/ligation
    CD
    conjugated dienes
    GSH
    glutathione
    GSSG
    oxidised glutathione
    LP
    lipid peroxides
    MDA
    malondialdehyde
    PF
    pair fed
    ROS
    reactive oxygen species
    SO
    sham operated
    TBARS
    thiobarbituric acid reactive substances
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  • Abbreviations used in this paper

    BDL/CBDL
    (chronic) bile duct ligated/ligation
    CD
    conjugated dienes
    GSH
    glutathione
    GSSG
    oxidised glutathione
    LP
    lipid peroxides
    MDA
    malondialdehyde
    PF
    pair fed
    ROS
    reactive oxygen species
    SO
    sham operated
    TBARS
    thiobarbituric acid reactive substances
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