The Role of Vitamin E in the Hepatotoxicity by Glutathione Depleting Agents

  • Alessandro F. Casini
  • Emilia Maellaro
  • Barbara Del Bello
  • Mario Comporti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 264)


During the last decades it has been recognized (1–3) that peroxidation of cellular membranes is an important event in the pathogenetic mechanisms of the liver injury induced by chemicals, such as CC14 or BrCCl3 , which give, upon metabolism, reactive free radicals. The latter ones alkylate cellular macromolecules but do not induce glutathione (GSH) depletion. It was subsequently shown (4–9) that lipid peroxidation is also strictly associated with the liver necrosis induced by chemi cals, such as bromobenzene and acetaminophen, which are converted to electrophilic intermediates giving extensive GSH conjugation and consequent GSH depletion. We have studied in particular the liver injury producedin vivo by three prototypical GSH depleting agents which undergo different fates in the liver cell: i) bromobenzene, that is metabolized by the microsomal monooxygenase system with consumption of NADPH (10–12); ii) allyl alcohol that is metabolized by the cytosolic enzyme alcohol dehydrogenase to acrolein and by aldehyde dehydrogenase to acrylic acid, with production of NADH (13,14); iii) and diethylmaleate which is mainly conjugated with GSH by GSH-transferases without previous metabolism (15).


Basal Diet Deficient Diet Allyl Alcohol Dehydroascorbic Acid Liver Necrosis 


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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Alessandro F. Casini
    • 2
  • Emilia Maellaro
    • 1
  • Barbara Del Bello
    • 1
  • Mario Comporti
    • 1
  1. 1.Istituto di Patologia GeneraleUniversità di SienaSienaItaly
  2. 2.Dipartimento di Medicina Sperimentale e Scienze BiochimicheUniversità di PerugiaPerugiaItaly

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