Lipid Peroxidation, Protein Thiols and Calcium Homeostasis in Bromobenzene-Induced Liver Damage

  • A. F. Casini
  • E. Maellaro
  • A. Pompella
  • M. Ferrali
  • M. Comporti
Part of the Basic Life Sciences book series (BLSC, volume 49)

Abstract

Previous studies from our laboratory1 have shown that bromobenzene or iodobenzene administration to mice results in the development of lipid peroxidation when the hepatic glutathione (GSH) depletion reaches critical values. Liver necrosis behaves similarly and strictly correlates with the extent of lipid peroxidation. The treatment of the intoxicated animals with Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a lower homolog of vitamin E, completely prevented both lipid peroxidation and necrosis, while not changing at all the extent of the covalent binding of bromobenzene metabolites to liver protein. This would suggest that lipid peroxidation is an important factor in the pathogenesis of the bromobenzene-induced liver cell death.

Keywords

Hydrolysis Toxicity Benzene Glutathione Adenosine 

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References

  1. 1.
    A. F. Casini, A. Pompella, and M. Comporti, Liver glutathione induced by bromobenzene, iodobenzene, and diethylmaleate poisoning and its relation to lipid peroxidation and necrosis, Am.J.Path. 118:225 (1985).PubMedGoogle Scholar
  2. 2.
    G. Bellomo, S. A. Jewell, M. T. Smith, H. Thor, and S. Orrenius, Perturbation of Ca2+ homeostasis during hepatocyte injury, in: “Mechanisms of Hepatocyte Injury and Death,” D. Keppler, H. Popper, L. Bianchi, and W. Reutter, eds., MTP Press Limited, Lancaster (1984).Google Scholar
  3. 3.
    G. Bellomo and S. Orrenius, Altered thiol and calcium homeostasis in oxidative hepatocellular injury, Hepatology 5:876 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    D. Di Monte, G. Bellomo, H. Thor, P. Nicotera, and S. Orrenius, Menadione-induced cytotoxicity is aassociated with protein thiol oxidation and alteration in intracellular Ca2+ homeostasis, Archs.Biochem.Biophys. 235:343 (1984).CrossRefGoogle Scholar
  5. 5.
    M. Moore, H. Thor, G. Moore, S. Nelson, P. Moldeus, and S. Orrenius, The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+, J.Biol.Chem. 260:13035 (1985).PubMedGoogle Scholar
  6. 6.
    J. Sedlak and R. H. Lindsay, Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent, Analyt. Biochem. 25:192 (1968).PubMedCrossRefGoogle Scholar
  7. 7.
    A. F. Casini, M. Ferrali, A. Pompella, E. Maellaro, and M. Comporti, Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice, Am.J.Path. 123:520 (1986).PubMedGoogle Scholar
  8. 8.
    A. Benedetti, R. Fulceri, M. Ferrali, L. Ciccoli, H. Esterbauer, and M. Comporti, Detection of carbonyl functions in phospholipids of liver microsomes in CCl4- and BrCCl3-poisoned rats, Biochim. Biophys.Acta 712:628 (1982).CrossRefGoogle Scholar
  9. 9.
    L. Moore, T. Chen, H. R. Knapp Jr., and E. J. Landon, Energy-dependent calcium sequestration activity in rat liver microsomes, J.Biol.Chem. 250:4562 (1975).PubMedGoogle Scholar
  10. 10.
    J. Bielawski and A. L. Lehninger, Stoichiometric relationships in mitochondrial accumulation of calcium and phosphate supported by hydrolysis of adenosine triphosphate, J.Biol.Chem. 241:4316 (1966).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • A. F. Casini
    • 1
  • E. Maellaro
    • 1
  • A. Pompella
    • 1
  • M. Ferrali
    • 1
  • M. Comporti
    • 1
  1. 1.Istituto di Patologia GeneraleUniversità di SienaSienaItaly

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