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Biological Reactive Intermediates—II pp 575–589Cite as

Free Radicals as Reactive Intermediates in Tissue Injury

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 136))

Abstract

My interest in free radicals as reactive intermediates, which are capable of initiating tissue injury, developed from studies with CCl4 in 1963. Whilst attempting to understand the mechanism of action of various substances that protect against certain aspects of the liver injury produced by CCl4 I was impressed by the fact that several of these ‘protective agents’ were free radical scavengers. One such ‘protective agent’ and free radical scavenger is the phenothiazine derivative Promethazine (or Phenergan) which had been reportedl in 1961 to decrease the liver necrosis resulting from CCl4 administration to rats. That observation by Rees and Spector was the stimulus for me to start a long-term investigation on liver protective substances; we have now accumulated data on the effectiveness (or not) of more than 60 free radical scavengers in relation to the liver disturbances caused by CCl4 in vivo and in vitro. In this article, however, I will concentrate mainly on specific experiments involving Promethazine to make some general points about the hepatotoxicity of CCl4.

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References

  1. K. R. Rees and W. G. Spector, Reversible nature of liver cell damage due to Carbon Tetrachloride as demonstrated by the use of Phenergan, Nature Lond., 190: 821 (1961).

    CAS  Google Scholar 

  2. M. Comporti, Inibizione da CCl4 in vitro ed in vivo della perossidazione lipidica, Boll.Soc.ital.Biol.Sper. 41: 222 (1964).

    Google Scholar 

  3. M. Comporti, C. Saccocci and M. U. Dianzani, Effect of CC14 in vitro and in vivo on lipid peroxidation of rat liver homogenates and subcellular fractions, Enzymologia 29: 185 (1965).

    CAS  PubMed  Google Scholar 

  4. A. K. Ghoshal and R. O. Recknagel, Positive evidence of acceleration of lipoperoxidation in rat liver by carbon tetrachloride: in vitro experiments, Life Sci. 4: 1521 (1965).

    CAS  Google Scholar 

  5. T. F. Slater, Stimulatory effect of CC14 in vitro on lipid peroxidation in rat liver microsomes, Proc.4th FEBS meeting, Oslo, Abstract 216 (1967).

    Google Scholar 

  6. R. O. Recknagel and E. A. Glende, Carbon tetrachloride hepatotoxicity: an example of lethal cleavage, CRC Critical Reviews in Toxicology, 2: 263 (1973).

    Article  Google Scholar 

  7. M. U. Dianzani and G. Ugazio, Lipid Peroxidation, in “Biochemical Mechanisms of Liver Injury”, T.F.Slater, ed. Academic Press, London (1978).

    Google Scholar 

  8. A. Benedetti, A. F. Casini, M. Ferrali and M. Comporti, Effects of diffusible products of peroxidation of rat liver microsomal lipids, Biochem.J., 180: 303 (1979).

    Article  CAS  Google Scholar 

  9. T. F. Slater in: “Free Radical Mechanisms in Tissue Injury”, Pion Ltd., London (1972).

    Google Scholar 

  10. J. F. Mead, Free radical mechanisms of lipid damage and consequences for cellular membranes, in: “Free Radicals in Biology, volume I”, W.A.Pryor, ed., Academic Press Inc., New York (1976).

    Google Scholar 

  11. 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 

  12. T. F. Slater, The inhibitory effects in vitro of phenothiazines and other drugs on lipid peroxidation systems in rat liver microsomes, and their relationship to the liver necrosis produced by carbon tetrachloride, Biochem.J. 106: 155 (1968).

    CAS  PubMed  Google Scholar 

  13. K. H. Cheeseman and T. F. Slater, Effects of selective agents on CC14-stimulated lipid peroxidation and covalent binding in rat microsomes, submitted to FEBS Letters (1980).

    Google Scholar 

  14. C. J. Reddrop, K. H. Cheeseman, J. Wagner, V. Kresni and T. F. Slater, Correlations between common tests for assessment of liver damage: screening for hepato-protective activity of Promethazine in carbon tetrachloride hepatotoxi city

    Google Scholar 

  15. D. Nadeau and C. Marchand, Importance of the route of administration of CC14 on the protective effect of Promethazine, Biochem.Pharmac. 22: 1250 (1973).

    CAS  Google Scholar 

  16. C. J. Reddrop, W. Riess and T. F. Slater, Interactions of carbon tetrachloride and Promethazine in the rat: I kinetics of CC14 blood and liver concentrations and CHC1, production, submitted to Biochem.Pharmacol. (1980).

    Google Scholar 

  17. G. Ugazio, Halogenoalkanes and Liver Injury, in: “Biochemical Mechanisms of Liver Injury”, T.F.Slater, ed., Academic Press, London (1978).

    Google Scholar 

  18. R. L. Willson, Free Radicals and Tissue Damage: Mechanistic Evidence from Radiation Studies“, in: Biochemical Mechanisms of Liver Injury”, T.F.Slater, ed., Academic Press, London (1978).

    Google Scholar 

  19. J. E. Packer, T. F. Slater and R. L. Willson, Reactions of the Carbon tetrachloride-related peroxy free radical (CC1,02) with amino acids: pulse radiolysis evidence, Life Sci. 23: 2617 (1978).

    Google Scholar 

  20. J.E. Packer, T. F. Slater and R. L. Willson (1980) to be published.

    Google Scholar 

  21. N. Vanderkooi and W. B. Fox, ESR study of the phorolysis of CF, OF and CF, OOCF3 at low temperature: the CF, 00• radical in solution, J.Chem.Phys. 47: 3634 (1967).

    CAS  Google Scholar 

  22. C. Hesse, N. Leray and J. Ronciu, Etude par résonance paramagnétique électronique de la structure du radical 13CC13, Molec.Physics 22: 137 (1971).

    CAS  Google Scholar 

  23. 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 Trans. II, 296 (1980).

    Article  Google Scholar 

  24. J. E. Packer, J. S. Mahood, V. 0. Mora-Arellano, T. F. Slater, R. L. Willson and B. S. Wolfenden, Free radicals and singlet oxygen scavengers: reactions of a peroxy-radical with 8-carotene, diphenylfuran and diazobicyclo-octane, Biochem. Biophys.Res.Commun., submitted (1980).

    Google Scholar 

  25. T. F. Slater, Biochemical Pathology in Microtime, in: “Recent Advances in Biochemical Pathology: Toxic Liver Injury”, M. U.Dianzani, G. Ugazio and L.M.Sena, eds., Minerva Medica Torino, 1976.

    Google Scholar 

  26. K. U. Ingold, Rate Constants for Free Radical Reactions in Solutions, in: “Free Radicals, volume I”, J.K.Kochi, ed., John Wiley and Sons, New York (1973).

    Google Scholar 

  27. C.Walling, in: “Free Radicals in Solution”, John Wiley, New York (1957).

    Google Scholar 

  28. A. Ingall, K. A. K. Lott, T. F. Slater, S. Finch and A. Stier, Metabolic Activation of carbon tetrachloride to a free radical product: studies using a spin trap, Biochem.Soc. Trans., 6: 962 (1978).

    CAS  PubMed  Google Scholar 

  29. M. J. Perkins, P. Ward and A. Horsfield, A probe for homolytic reactions in solution, III, Radicals by hydrogen substitution, J.Chem.Soc. (B), 395 (1970).

    Google Scholar 

  30. 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 (1978).

    CAS  PubMed  Google Scholar 

  31. B. Kalyanaram, R. P. Mason, E. Perez-Reyes, C. F. Chignell, C. R. Wolf and R. M. Philpot, Characterisation of the free radical formed in aerobic microsomal incubations containing carbon tetrachloride and NADPH, Biochem.Biophys.Res.Commun. 89: 1065 (1979).

    Google Scholar 

  32. E. G. Janzen, A Critical Review of Spin Trapping in Biological Systems, in: “Free Radicals in Biology, vol.IV”, W.A.Pryor, ed., Academic Press Inc., New York (1980).

    Google Scholar 

  33. A. Tomasi, E. Albano, K. A. K. Lott and T. F. Slater, Spin trapping of free radical products of CCiq activation using pulse radiolysis and high energy radiation procedures, FEBS Letters, submitted (1980).

    Google Scholar 

  34. J. L. Poyer, P. B. McCay, E. K. Lai, E. G. Janzen and E.R. Davis, 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 (1980).

    Google Scholar 

  35. T. F. Slater and B. C. Sawyer, The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro: general features of the systems used, Biochem.J., 123: 805 (1971).

    Article  CAS  Google Scholar 

  36. G. Poli, E. Gravela, E. Albano and M. U. Dianzani, Studies on fatty liver with isolated hepatocytes, II: The action of carbon tetrachloride on lipid peroxidation, protein, and triglyceride synthesis and secretion, Exp.Molec.Pathol., 30: 116 (1979).

    Article  CAS  Google Scholar 

  37. E. Schauenstein, H. Esterbauer and H. Zollner, in “Aldehydes in Biological Systems”, Pion Ltd., London (1977).

    Google Scholar 

  38. H. Esterbauer, M. Comporti and A. Benedetti, Biochemical effects of 4-hydroxyalkenals in particular 4-hydroxynonenal produced by microsomal lipid peroxidation, Amer.Soc.Oil Chemists World Congr. Abstract 222, New York (1980).

    Google Scholar 

  39. M. U.Dianzani and L. Paradisi, in press (1980).

    Google Scholar 

  40. T. F. Slater and B. C. Sawyer, 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 (1971).

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Biochemistry Department, Brunel University, Uxbridge, Middx., UK

    T. F. Slater

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  1. T. F. Slater
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Editor information

Editors and Affiliations

  1. Rutgers University, Piscataway, New Jersey, USA

    Robert Snyder , Charlotte M. Witmer  & Beatrice N. Engelsberg ,  & 

  2. Medical University of South Carolina, Charleston, South Carolina, USA

    David J. Jollow  & Stephen L. Longacre  & 

  3. University of Surrey, Guildford, Surrey, England

    Dennis V. Parke  & C. Gordon Gibson  & 

  4. Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    James J. Kocsis  & George F. Kalf  & 

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© 1982 Springer Science+Business Media New York

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Slater, T.F. (1982). Free Radicals as Reactive Intermediates in Tissue Injury. In: Snyder, R., et al. Biological Reactive Intermediates—II. Advances in Experimental Medicine and Biology, vol 136. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-0674-1_42

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  • DOI: https://doi.org/10.1007/978-1-4757-0674-1_42

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  • Print ISBN: 978-1-4757-0676-5

  • Online ISBN: 978-1-4757-0674-1

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