Antioxidants and Prevention of the Hepatocellular Damage Induced by Glutathione-Depleting Agents

  • A. F. Casini
  • E. Maellaro
  • B. Del Bello
  • M. Comporti
Part of the Developments in Oncology book series (DION, volume 67)


Previous studies from our laboratory (1–3) have shown that the intoxication of mice with three prototypical glutathione (GSH) depleting agents (bromobenzene, diethylmaleate and allyl alcohol) is followed by the development of lipid peroxidation and liver necrosis after the hepatic GSH depletion has reached critical values. The treatment of the intoxicated animals with the antioxidants Trolox C or desferrioxamine, completely prevents both lipid peroxidation and liver necrosis, while not changing at all the extent of the covalent binding of bromobenzene metabolites to liver protein. In subsequent studies, the relationships among the various antioxidant systems (namely, vit. E, GSH and ascorbic acid) of the liver cell have been investigated under conditions of severe GSH depletion, like those induced by the GSH depleting agents mentioned above. Such an abrupt loss of the GSH antioxidant system could reasonably affect the other antioxidant systems. According to some authors (4,5), in fact, GSH is directly involved in the enzymatic system (“tocopheroxy radical reductase“) that reduces the oxidized form of tocopherol; on the other hand, according to others (6,7) the tocopherol regenerating system consists of ascorbic acid that is converted in the reaction to semidehydroascorbic acid radical and then to dehydroascorbic acid. Even in the latter case GSH may be involved in the reduction of the oxidized form of ascorbic acid (dehydroascorbic acid) (8,9). Alternatively, GSH depletion could affect the other antioxidant systems, by decreasing the disposition of hydrogen peroxide through GSH peroxidase. Vit. E may be consumed as a result of an increased formation of lipid peroxides in cell membranes, while ascorbate may be involved by direct interactions with oxy-radicals, especially with hydroxyl radicals.


Lipid Peroxidation Antioxidant System Basal Diet Allyl Alcohol Dehydroascorbic Acid 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • A. F. Casini
    • 1
  • E. Maellaro
    • 1
  • B. Del Bello
    • 1
  • M. Comporti
    • 1
  1. 1.Istituto di Patologia GeneraleUniversita di SienaSienaItaly

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