Lipid Peroxidation in Experimentally Produced Liver Injury, Liver Tumors and in Liver Regeneration

  • T. F. Slater
Part of the NATO ASI Series book series (NSSA, volume 189)


Lipid peroxidation is a free radical-mediated process leading to an oxidative degradation of lipid materials including triglycerides, phospholipids, cholesterol and its esters, and unsaturated fatty acids. It may be a non-enzymic process (eg. following the impact of radiation or with a transition metal-catalysed reaction) or it may be catalysed by enzymes, either specifically as with cyclo-oxygenase and lipoxygenases, or nonspecifically as with the role of the NADPH-cytochrome P450 reductase in maintaining an iron chelate in a reduced state.1 In this article lipid peroxidation will be considered in relation to the peroxidation of polyunsaturated fatty acids (PUFA’s), both free and esterified. More general background reviews on lipid peroxidation that may be consulted for reference are references 2,3.


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  1. 1.
    P. Hochstein, K.Nordenbrand and L.Ernster, Evidence for the involvement of iron in the ADP-activated peroxidation of lipids in microsomes and mitochondria, Biochem. Biophys. Res. Commun. 14: 323328 (1964).CrossRefGoogle Scholar
  2. 2.
    M. Comporti, Biology of disease. Lipid peroxidation and cellular damage in toxic liver injury, Lab. Invest. 53: 599–623 (1985).PubMedGoogle Scholar
  3. 3.
    D. L Tribble, T. Y. Aw and D. P. Jones, The pathophysiological significance of lipid peroxidation in oxidative cell injury, Hepatology 7: 377–386.CrossRefGoogle Scholar
  4. 4.
    T. L. Dormandy, Free radical activity and diene conjugation in man, in “Free Radicals in Liver Injury”, G. Poli, K. H. Cheeseman, M. U. Dianzani and T. F Slater, eds. IRL Press, Oxford, 167–173, (1985).Google Scholar
  5. 5.
    C. S. Foote, Mechanism of addition of singlet oxygen to olefins and other substances, Pure Appl. Chem. 27:635, (1971)Google Scholar
  6. 6.
    T. F. Slater, Free radical mechanisms in tissue injury, Pion, London, 1–283 (1972).Google Scholar
  7. 7.
    W. A. Pryor, Free Radicals, McGraw Hill Book Co., New York, 1–354 (1966).Google Scholar
  8. 8.
    M. Davies and T. F Slater, Electron spin resonance spin trapping studies on the photolytic generation of halocarbon radicals, Chem. Biol. Interactions, 58: 137–147 (1986).CrossRefGoogle Scholar
  9. 9.
    H. F. Blum, Photodynamic action and diseases caused by light, Hafner, New York, 1–309 (1964).Google Scholar
  10. 10.
    I. H. Magnus, Dermatological Photobiology, Blackwells, Oxford, 1–292,(1976)Google Scholar
  11. 11.
    T. F. Slater and P. A. Riley, Photosensitisation and Lysosomal Damage, Nature,Lond., 209: 151–154 (1966).CrossRefGoogle Scholar
  12. 12.
    R. K. Clayton, “Light and Living Matter: A Guide to the Study of Photobiology. Volume 2: The Biological Part”, 1–243 (1971).Google Scholar
  13. 13.
    D. Kessel and T J Dougherty (eds), Porphyrin Photosensitization, Plenum Press, New York, 1–294 (1983).Google Scholar
  14. 14.
    T. F. Slater, Necrogenic action of carbon tetrachloride in the rat: a speculative mechanism based on activation, Nature Lond., 209: 36–40 (1966).Google Scholar
  15. 15.
    J. R. Mitchell, S. D. Nelson, S. S. Thorgeirsson, R. J. McMurtry and E. Dybing, Metabolic Activation: Biochemical basis for many drug-induced liver injuries, H. Popper and F. Schaffner eds, Progr.Google Scholar
  16. Liver Disease 5:259–279, Grune and Stratton, New York (1976).Google Scholar
  17. 16.
    M. A. Trush, E. G. Mimnaugh and T. E. Gram, Activation of pharmacological agents to radical intermediates. Implications for the role of free radicals in drug action and toxicity, Biochem. Pharmacol. 31:3335–3346 (1982).Google Scholar
  18. 17.
    R. O. Recknagel, Carbon tetrachloride toxicity, Pharmacol. Rev. 19: 145–208 (1967).Google Scholar
  19. 18.
    T. F. Slater, Activation of carbon tetrachloride: chemical principles and biological significance, in “Free radicals, lipid peroxidation and cancer”, D. C. H. McBrien and T. F. Slater eds, Academic Press, London, 243–270 (1982).Google Scholar
  20. 19.
    T. F. Slater, K. H. Cheeseman and K. U. Ingold, Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury, Phil. Trans. R. Soc. Lond B311: 633–645 (1985).CrossRefGoogle Scholar
  21. 20.
    M. U. Dianzani and G. Ugazio, Lipid peroxidation in “Biochemical Mechanisms of Liver Injury”, T. F. Slater ed., Academic Press, London, 669–707 (1978).Google Scholar
  22. 21.
    G. R. Cameron and W. A. E. Karunaratne, Carbon tetrachloride cirrhosis in relation to liver regeneration, J. Path. Bact. 42: 1–21 (1936).CrossRefGoogle Scholar
  23. 22.
    E. A. Smuckler, 0.A.Iseri and E. P. Benditt, An intracellular defect in protein synthesis induced by carbon tetrachloride, J. Exp. Med. 116: 55–72, (1962)CrossRefGoogle Scholar
  24. 23.
    J. L. Poyer, R. A. Floyd, P. B. McCay, E. G. Janzen and E. R. Davis, Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane, Biochim. Biophys. Acta 539:402–409 (1978).CrossRefGoogle Scholar
  25. 24.
    E. Albano, K. A. K. Lott, T. F. Slater, A. Stier, M. C.R. Symons and A. Tomasi, Spin-trapping studies on the free-radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions, isolated hepatocytes and in vivo in the rat, Biochem J. 204: 593–603 (1982).Google Scholar
  26. 25.
    T. F. Slater, A note on the relative toxic activities of tetrachloromethane and trichlorofluoromethane on the rat, Biochem. Pharmacol. 14: 178–181 (1965).CrossRefGoogle Scholar
  27. 26.
    R. N. Le Page, K. H. Cheeseman, N. Osman and T. F. Slater, Lipid per-oxidation in purified plasma membrane fractions of rat liver in relation to the hepatotoxicity of carbon tetrachloride, Cell Biochemistry and Function 6: 87–99 (1988).Google Scholar
  28. 27.
    R. Carini, K. H. Cheeseman and T. F. Slater, Morphological and biochemical studies on the effects of carbon tetrachloride and trichlorofluoromethane on isolated rat hepatocytes, (unpublished data, 1989 ).Google Scholar
  29. 28.
    M. L. Berger, H. Bhatt, B. Combes and R W Estabrook, CC14-induced toxicity in isolated hepatocytes: the importance of direct solvent injury, Hepatology 6: 36–45 (1986).Google Scholar
  30. 29.
    T. C. Butler, Reduction of carbon tetrachloride in vivo and reduction of carbon tetrachloride and chloroform in vitro by tissues and tissue constituents, J. Pharmacol. Exp. Therap. 134: 311–319 (1961).Google Scholar
  31. 30.
    M. Comporti, C. Saccocci and M. U. Dianzani, Effect of CC14 in vitro and in vivo on lipid peroxidation of rat liver homogenates and sub-cellular fractions, Experientra 29: 185–204, (1965).Google Scholar
  32. 31.
    A. K. Ghoshal and R. 0. Recknagel, Positive evidence of acceleration of lipoperoxidation in rat liver by carbon tetrachloride: in vitro experiments, Life Sciences 4: 1521–1530 (1965).PubMedGoogle Scholar
  33. 32.
    T. F. Slater, In vitro effects of carbon tetrachloride on rat liver microsomes, Biochem. J., 101:16–17P (1966).Google Scholar
  34. 33.
    T. F. Slater, Stimulatory effects of CC14 in vitro on lipid peroxi-Google Scholar
  35. dation in rat liver microsomes, Proc. 4th FEES Symposium, Oslo; Abstract 214 (1967)Google Scholar
  36. 34.
    M. Comporti, E. Burdino and G. Ugazio, Alterazioni della composizione in acidi grassi dei lipidi del fegato e dei microsomi epatici nel ratto intossicato contetracloruro di carbonio, Boll. Soc. Ital. Biol. Sper., 45: 700–703 (1969).Google Scholar
  37. 35.
    C. D. Klaassen and G. L. Plaa, Comparison of the biochemical alterations elicited in livers from rats treated with carbon tetrachloride, chloroform, 1,1,2-trichloroethane and 1,1,1-trichloroethane, Biochem. Pharmacol. 18:2019–2027 (1969).Google Scholar
  38. 36.
    P. J. Jose and T. F. Slater, Increased concentrations of malonaldehyde in the livers of rats treated with carbon tetrachloride, Biochem. J., 128: 141P (1972).Google Scholar
  39. 37.
    C. A. Riely, G. Cohen and M. Lieberman, Ethane Evolution: A new index of lipid peroxidation, Science 183: 208–210 (1974).PubMedGoogle Scholar
  40. 38.
    J. S. L. Fowler, Carbon tetrachloride metabolism in the rabbit, Brit. J. Pharmacol. 37: 733–737 (1969).Google Scholar
  41. 39.
    J. E. Packer, T. F. Slater and R. L. Willson, Reactions of the carbon tetrachloride-related peroxy free radical (CC1302•) with amino acids: pulse radiolysis evidence, Life Sciences 23: 2617–2620, (1978).CrossRefGoogle Scholar
  42. 40.
    J. Monig, D. Barnemann and K D Asmus, One electron reduction of CC14 in oxygenated aqueous solutions: a CC1302•-free radical mediated formation of Cl-and CO2, Chem. Biol. Interactions 45:15–27 (1983).CrossRefGoogle Scholar
  43. 41.
    R. L. Willson, Electrophilic free radicals and nucleic acid damage: pulse radiolysis studies, Panminerva Medica 18: 391–402 (1976).PubMedGoogle Scholar
  44. 42.
    J. E. Packer, R. L. Willson, D. Bahnemann and K. D. Asmus, Electron transfer reactions of halogenated aliphatic peroxyl radicals: measurement of absolute rate constants by pulse radiolysis, J. Chem. Soc. Perkin II 296–299 (1980).Google Scholar
  45. 43.
    K. O. Hiller, P. L. Hodd and R. L. Willson, Anti-inflammatory drugs: protection of a bacterial virus as an in vitro biological measure of free radical activity, Chem. Biol. Int., 47:293–305 (1983).CrossRefGoogle Scholar
  46. 44.
    L. G. Forni, J. E. Packer, T. F. Slater and R. L. Willson, Reactions of the trichloromethyl and halogen-derived peroxy radicals with unsaturated fatty acids: a pulse radiolysis study, Chem. Biol. Interactions 45:171–177 (1983).Google Scholar
  47. 45.
    T. F. Slater, K. H. Cheeseman, M. J. Davies and J. S. Hurst, Free radical mechanisms in relation to cell injury and cell division, in “Drug Metabolism: from Molecules to Man”, D. J. Benford, J. W. Bridges and G. G. Gibson eds., Taylor and Francis, London, 679–689, (1987).Google Scholar
  48. 46.
    T. F. Slater and K. H. Cheeseman, Free radical mechanisms of tissue injury and mechanisms of protection in “Reactive Oxygen Species in Chemistry, Biology and Medicine”, Q. Quintanilha ed., 1–14 (1988).Google Scholar
  49. 47.
    T. F. Slater, Free radical scavengers in “International workshop on (+)- cyanidanol-3 in diseases of the liver”, H. O. Conn ed, Royal Society of Medicine Int. Congress and Symposium, Series No.47, Royal Society of Medicine, London, 11–15 (1981).Google Scholar
  50. 48.
    T. F. Slater, Free Radical Mechanisms in Tissue Injury, Biochem. J. 222: 1–15 (1984).Google Scholar
  51. 49.
    M. E. Hemler, H. W. Cook and W. E. M. Lands, Prostaglandin synthesis can be triggered by lipid peroxides, Archs. Biochem. Biophys.193 340–345 (1979).Google Scholar
  52. 50.
    G. D. Snyder, J. Capdevila, N. Chacos, S. Manna and J. R. Falck, Action of luteinizing hormone - releasing hormone: involvement of novel arachidonic acid metabolites, Proc. Natn. Acad. Sci. U.S.A., 80: 3504–3507 (1983).CrossRefGoogle Scholar
  53. 51.
    H. Esterbauer, H. Zollner and R. J. Schaur, Hydroxyalkenals: cytotoxic products of lipid peroxidation, ISI Atlas of Science: Biochemistry 311–317 (1988).Google Scholar
  54. 52.
    T. F. Slater, Biochemical Pathology in Microtime, Panminerva Medica 18: 381–390 (1976).PubMedGoogle Scholar
  55. 53.
    T. F. Slater, C. Benedetto, G. W. Burton, K. H. Cheeseman, K. U. Ingold and J. T. Nodes, Lipid peroxidation in animal tumours: a disturbance in the control of cell division? in “Icosanoids and Cancer, H. Thaler-Dao, A. Crastes de Paulet and R. Paoletti eds., Raven Press, New York, 21–29 (1984).Google Scholar
  56. 54.
    K. H. Cheeseman, M. Collins, K. Proudfoot, T. F. Slater and G. W. Burton, A. C. Webb and K. U. Ingold, Studies on lipid peroxidation in normal and tumour tissues. The Novikoff rat liver tumour, Biochem. J., 235:507–514 (1986).CrossRefGoogle Scholar
  57. 55.
    K. H. Cheeseman, S. Emery, S. P. Maddix, T. F. Slater, G. W. Burton and K. U. Ingold, Studies on lipid peroxidation in normal and tumour tissues. The Yoshida rat liver tumour, Biochem. J., 250: 247–252 (1988)PubMedGoogle Scholar
  58. 56.
    S. Emery, K. H. Cheeseman and T. F. Slater, Effects of vitamin E deficiency on the growth in vivo of the Yoshida rat liver tumour in the rat (unpublished data, 1989 ).Google Scholar
  59. 57.
    M. R, Allison, Regulation of hepatic growth, Physiol. Revs., 66: 499–541 (1986).Google Scholar
  60. 58.
    H. A. Hopkins, H. A. Campbell, B. Barbiroli and R. Van Potter, Thymidine kinase and deoxyribonucleic acid metabolism in growing and regenerating livers from rats on controlled feeding schedules. Biochem. J. 136: 955–966 (1973).PubMedGoogle Scholar
  61. 59.
    K. H. Cheeseman, M. Collins, S. Maddix, A. Milia, K. Proudfoot, T. F. Slater, G. W. Burton, A. Webb and K. U. Ingold, Lipid peroxidation in regenerating rat liver, FEBS Letters 209:191–196 (1986).CrossRefGoogle Scholar
  62. 60.
    T. F. Slater, K. H. Cheeseman, S. Emery, S. Maddix, M. Collins and A. Milia, Lipid peroxidation and thymidine kinase activity in regenerating rat liver: correlation of changes in time (unpublished data, 1989 ).Google Scholar
  63. 61.
    T. F. Slater, K. H. Cheeseman, C. Benedetto, M. Collins, S. Emery, S. P. Maddix, J. T. Nodes, K. Proudfoot, G. W. Burton, A. Webb and K. U. Ingold, Studies on the hyperplasia (regeneration) of the rat liver following partial hepatectomy: changes in lipid peroxidation and general biochemical aspects (submitted for publication, 1989 ).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • T. F. Slater
    • 1
  1. 1.Dept. of Biology and BiochemistryBrunel UniversityUxbridge, MiddxUK

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