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Mitochondria in Alcoholic Liver Disease

  • José C. Fernández-Checa
  • Carmen García-Ruiz
  • Anna Colell
Chapter
  • 158 Downloads

Conclusion

Mitochondria generate ROS as byproducts of aerobic respiration. When the availability of free radicals is controlled, ROS act as signaling intermediates, regulating nuclear gene expression by activating transcription factor NFKB. The GSH redox cycle plays a critical role in controlling certain ROS, especially hydrogen peroxide, because mitochondria lack catalase. Hence not only the presence of reduced GSH but a precise balance between antioxidant enzymes such as MnSOD and GSH peroxidese guarantees adequate hydrogen peroxide levels. Limiting mitochondrial GSH may result in uncontrolled ROS generation, which can initiate escalating cell damage. Alcohol-induced depiction of mitochondrial GSH sensitizes hcpatocytes to the toxic effects of tumor necrosis factor by amplifying mitochondrial ROS generation, which not only promotes cell death but also increases the expression of cytokines, including TNF, that can further act in parenchymal cells in an autocrine fashion, establishing a deadly vicious cycle. Replenishing mitochondrial GSH by different strategics (in vivo administration of S-adenosyl-L-methionine; in vitro by GSH-ethylester) both attenuates the lethal effect of oxidative stress and down-regulates expression of cytokines. Based on these observations, beneficial effects can be expected from therapeutic strategies targeted to increase selective antioxidant defenses in mitochondria.

Keywords

Alcoholic Liver Disease Chronic Ethanol Ethanol Oxidation Mitochondrial Electron Transport Chain Fatty Acid Ethyl Ester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • José C. Fernández-Checa
    • 1
  • Carmen García-Ruiz
    • 1
  • Anna Colell
    • 1
  1. 1.Liver Unit, Departments of Medicine and GastroenterologyHospital Clinic i Provincial, Institute Investigaciones Biomedicas August Pi I Suñer, Consejo Superior Investigaciones CientificasBarcelonaSpain

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