The contribution of covalent binding and lipid peroxidation in the pathogenesis of fatty liver by CCl4

  • M. U. Dianzani
  • U. M. Marinari
  • G. Poli


It is now well known that CCl4 is metabolised by the smooth endoplasmic reticulum of liver cell with the production of the trichloromethyl radical (CCI3) (Slater, 1978). The direct demonstration of the generation of such a reactive metabolite has been given by electron spin resonance studies (Tomasi et al., 1980; Poyer et al., 1980). In addition, with pulse radiolysis techniques, the rapid conversion of CCI3, in the presence of O2, into CCl3O2, the trich-loromethylperoxy radical, has been demonstrated (Packer et al., 1978,1980).


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. BENEDETTI, A., CASINI, A.F., FERRALI, M. & COMPORTI, M. (1977). Studies on the relationships between carbon tetrachloride-induced alterations of liver microsomal lipids and impairment of glucose-6-phosphatase activity. Exp. mol Pathol, 27, 309–323.CrossRefGoogle Scholar
  2. BERGERON, J.J.M., EHRENREICH, SIEKEVITZ, P. & PALADE, G.E. (1973). Golgi fractions prepared from rat liver homogenates. II. Biochemical characterization. J. Cell Biol, 59, 73–88.CrossRefGoogle Scholar
  3. BURSTEIN, M. & LEGMAN, P. (1982). In Lipoprotein Precipitation. Burstein, M. (ed.), Basel: Karger.Google Scholar
  4. CADENAS, E., MÜLLER, A., BRIGELIUS, R., ESTER-BAUER, H. & SIES, H. (1983). Effects of 4-hydroxynonenal on isolated hepatocytes. Studies on chemiluminescence response, alkane production and glutathione status. Biochem. J, 214, 479–487.CrossRefGoogle Scholar
  5. CASTRO, J.A., DIAZ GOMEZ, M.I., de FERREIRA, E.C., de CASTRO, CR., D’ACOSTA, N. & de FENOS, O.M. (1972). Carbon tetrachloride effect on rat liver and adrenals related to their mixed function oxygenase content. Biochem. biophys. Res. Commun, 47, 315–321.CrossRefGoogle Scholar
  6. DIANZANI, M.U. (1981). In Recent Advances in Lipid Peroxidation and Tissue Injury, Slater, T.F. & Garner, A. (eds) pp. 133–155, Uxbridge, London: Brunei University Press.Google Scholar
  7. DIANZANI, M.U. (1982). In Free Radicals, Lipid Peroxidation and Cancer. McBrien, D.C.H. & Slater, T.F. (eds) pp. 129–158, London: Academic Press.Google Scholar
  8. DIANZANI, M.U., POLI, G., GRAVELA, E., CHIARPOTTO, E., ALBANO, E. (1981). Influence of lipid peroxidation on lipoprotein secretion by isolated hepatocytes. Lipids, 16, 823–829.CrossRefGoogle Scholar
  9. DIANZANI, M.U. & POLI, G. (1984). In Frontiers of Gastrointestinal Research Vol. 8. Gentilini, P. & Dian-zani, M.U. (eds) pp. 1–13, Basel: Karger.Google Scholar
  10. ESTERBAUER, H., CHEESEMAN, K.H., DIANZANI, M.U., POLI, G. & SLATER, T.F. (1982). Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe3+ in rat liver microsomes. Biochem. J., 208, 129–140.CrossRefGoogle Scholar
  11. GABRIEL, L., BONELLI, G. & DIANZANI, M.U. (1977). Inhibition of colchicine binding to rat liver tubulin by aldehydes and by linoleic acid hydroperoxide. Chem.-Biol Interactions, 19, 101–109.CrossRefGoogle Scholar
  12. GLENDE, E.A., HRUSZKEWYCZ, A.M. & RECKNAGEL, R.O. (1976). Critical role of lipid peroxidation in carbon tetrachloride-induced loss of aminopyrene demethylase, cytochrome P450 and glucose-6-phosphatase. Biochem. Pharmac, 25, 2163–2170.CrossRefGoogle Scholar
  13. GRAVELA, E. & DIANZANI, M.U. (1970). Studies on the mechanism of CCLrinduced polyribosomal damage. FEBS Lett., 9, 93–96.CrossRefGoogle Scholar
  14. GRAVELA, E., POLI, G., ALBANO, E. & DIANZANI, M.U. (1977). Studies on fatty liver with isolated hepatocytes. I. The action of Colchicine, Phalloidin, Cytochalasin B, and Cyclohexamide on protein and triglyceride synthesis and secretion. Exp. mol Pathol, 27, 339–352.CrossRefGoogle Scholar
  15. KUPFER, D. & ORRENIUS, S. (1970). Characteristics of guinea pig liver and adrenal monooxygenase systems. Mol Pharmac, 6, 221–230.Google Scholar
  16. PACKER, J.E., SLATER, T.F., WILLSON, R.L. (1978). Reactions of the carbon tetrachloride related peroxy free radical (CCI3O2) with amino acids: pulse radiolysis evidence. Life Sei., 23, 2617–2620.CrossRefGoogle Scholar
  17. PACKER, J.E., WILLSON, R.L., BAHNEMANN, D. & ASMUS, K.D. (1980). Electron transfer reactions of halogenated aliphatic peroxyl radicals: measurement of absolute rate constants by pulse radiolysis. J. chem. Soc. Perkin Trans., II, 296–299.CrossRefGoogle Scholar
  18. POLI, G., POLI CHIONO, M., SLATER, T.F., DIANZANI, M.U. & GRAVELA, E. (1978). Effects of carbon tetrachloride on isolated liver cells: stimulation of lipid peroxidation and inhibitory action of free radical scavengers. Biochem. Soc. Trans., 6, 589–591.CrossRefGoogle Scholar
  19. POLI, G., GRAVELA, E., ALBANO, E. & DIANZANI, M.U. (1979). Studies on fatty liver with isolated hepatocytes: II, the action of carbon tetrachloride on lipid peroxidation, protein and triglyceride synthesis and secretion. Exp. mol Pathol, 30, 116–127.CrossRefGoogle Scholar
  20. POLI, G., CHEESEMAN, K.H., SLATER, T.F. & DIANZANI, M.U. (1981). The role of lipid peroxidation in CC14 induced damage to liver microsomal enzymes: comparative studies in vitro using microsomes and isolated liver cells. Chem-Biol Interactions, 37, 13–24.CrossRefGoogle Scholar
  21. POLI, G. & GRAVELA, E. (1982). In Free Radicals, Lipid Peroxidation and Cancer, McBrien, D.C.H. & Slater, T.F. (eds) pp. 215–241, London: Academic Press.Google Scholar
  22. POYER, J.L., McCAY, P.B., LAI, E.K., JANZEN, E.G. & DAVIS, E.R. (1980). Confirmation of assignment of the trichloromethyl radical spin adduct detected by spin trapping during 13C-carbon tetrachloride metabolism in vitro and in vivo. Biochem. biophys. Res. Commun., 94, 1154–1160.CrossRefGoogle Scholar
  23. RECKNAGEL, R.O. (1967). Carbon tetrachloride hepatotoxicity. Pharmac. Rev., 19,145–208.Google Scholar
  24. RECKNAGEL, R.O., HRUSZKEWICZ, A. & GLENDE, E.A. (1976). In Advances in Biochemical Pathology. Toxic Liver Injury. Dianzani, M.U., Ugazio, G. & Sena, L.M. (eds), pp. 93–98, Torino: Minerva Medica.Google Scholar
  25. REYNOLDS, E.S. & MOSLEN, M.T. (1974). In vitro covalent binding of 14CC14 metabolites in liver microsomal lipids. Biochem. biophys. Res. Commun., 57, 747–750.CrossRefGoogle Scholar
  26. SCHAUENSTEIN, E., ESTERBAUER, H., ZOLLNER, H. (1977). In Aldehydes in Biological Systems. Their Natural Occurrence and Biological Activities, Lagnado, J.R. (ed.), London: Pion Ltd.Google Scholar
  27. SLATER, T.F. (1972). In Free Radical Mechanisms in Tissue Injury. Lagnado, J.R. (ed.) London: Pion Ltd.Google Scholar
  28. SLATER, T.F. (1978). In Biochemical Mechanisms of Liver Injury. Slater, T.F. (ed.), pp. 745–801, London: Academic Press.Google Scholar
  29. SLATER, T.F. (1982). In Free Radicals, Lipid Peroxidation and Cancer. McBrien, D.C.H. & Slater, T.F. (eds) pp. 243–274, London: Academic Press.Google Scholar
  30. SLATER, T.F. & SAWYER, B.C. (1971). The stimulatory effects of carbon tetrachloride on peroxidative reactions in rat liver fractions in vitro. Interaction sites in the endoplasmic reticulum. Biochem. J., 123, 815–821.CrossRefGoogle Scholar
  31. TOMASI, A., ALBANO, E., LOTT, K.A.K. & SLATER, T.F. (1980). Spin trapping of free radical products of CCl4 activation using pulse radiolysis and high energy radiation procedures. FEBS Lett., 122, 303–306.CrossRefGoogle Scholar

Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • M. U. Dianzani
    • 1
  • U. M. Marinari
    • 2
  • G. Poli
    • 1
  1. 1.Institute of General PathologyUniversity of TorinoTorinoItaly
  2. 2.Institute of General PathologyUniversity of GenovaGenovaItaly

Personalised recommendations