Free Radicals in Health and Disease: Implications for Drug Delivery and Targeting

  • Catherine Rice-Evans
Part of the NATO ASI Series book series (NSSA, volume 155)


Free radicals are essential to many normal biological processes, e.g. as intermediates in enzyme-catalysed reactions, in prostaglandin synthesis, in tissue response to invading micro-organisms, and yet can be highly destructive if not tightly controlled. Radicals species have been implicated in many diseased states (Table 1) (Halliwell, 1987). The question as to whether free radical reactions are a cause of tissue damage or an accompaniment to or a consequence of such injury is by no means clear as yet in many instances. However, what is clear is that diseased or damaged tissues undergo radical reactions more readily than normal tissues (Halliwell & Gutteridge, 1985a), thus exacerbating the primary lesion.


Lipid Peroxidation Hyaluronic Acid Respiratory Burst Lipid Hydroperoxide Peroxy Radical 
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  1. Aeschback, R., Amado, R., and Neukom, H., 1976, Formation of dityrosine crosslinks in proteins by oxidation of tyrosine residues, Biochim. Biophys.Acta, 439:292.Google Scholar
  2. Babior, B. M., 1978, Oxygen-dependent microbial killing by phagocytes, New Engl.J.Med., 298:659.PubMedCrossRefGoogle Scholar
  3. Davies, K., and Goldberg, A. L., 1987, Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes, J.Biol.Chem., 262:8220.PubMedGoogle Scholar
  4. Dean, R. T., Roberts, C. R., and Forni, L. G., 1984, Oxygen-centered free radicals can efficiently degrade the polypeptide of proteoglycans in whole cartilage, Biosci. 4:1017.CrossRefGoogle Scholar
  5. Esterbauer, H., 1985, in: “Free Radicals in Liver Injury,” G. Pol, K.H. Cheeseman, M.U. Dianzani, T.F. Slater, eds., pp. 29–47, IRL Press.Google Scholar
  6. Greenwald, R. A., and Moy, W. W., 1980, Effect of oxygen-derived free radicals on hyaluronic acid, Arthritis Rheum., 23:455.PubMedCrossRefGoogle Scholar
  7. Griffiths, H. R., Unsworth, J., Blake, D. R., and Lunec, J., 1987, Oxidation of amino acids within serum proteins, in: “Free Radicals, Chemical Mechanisms and Experimental Pathology,” C. Rice-Evans and T.L. Dormandy, eds., Richelieu Press, London, In press.Google Scholar
  8. Gutteride, J.M.C., 1984, Lipid peroxidation and possible hydroxyl radical formation stimulated by the self-reduction of a doxorubicin-iron (III) complex, Biochem.Pharmacol., 33:1725.CrossRefGoogle Scholar
  9. Halliwell, B., 1987, The measurement of free radical reactions in humans: Some thoughts for future experimentation, FEBS Lett., 213:9.PubMedCrossRefGoogle Scholar
  10. Halliwell, B., and Gutteridge, J.M.C., 1984, Oxygen toxicity, oxygen radicals, transition metals and disease, Biochem.J., 219:1.PubMedGoogle Scholar
  11. Halliwell, B., and Gutteridge, J.M.C., 1985a, The importance of free radicals and catalytic metal ions in human disease, Mol.Aspects Med., 8:89.CrossRefGoogle Scholar
  12. Halliwell, B., and Gutteridge, J.M.C., 1985b, “Free Radicals in Biology and Medicine,” Clarendon Press, Oxford.Google Scholar
  13. Halliwell, B., and Gutteridge, J.M.C., 1986, Iron and free radical reactions: Two aspects of antioxidant protection, Trends Biochem.Sci., 11:372.CrossRefGoogle Scholar
  14. Kappus, H., 1985, Lipid peroxidation: Mechanisms, analysis, enzymology and biological relevance, in: “Oxidative Stress,” H. Sies, ed., pp. 273–310, Academic Press, New York.Google Scholar
  15. Kleinweld, H. A., Biemond, P., Hack, C. E., Swaak, A. J. G., Koster, J., 1986, Free radicals, immunoglobulin G modification and rheumatoid arthritis, in: “Free Radicals and Arthritic Diseases,” A.J.G. Swaak and J.F. Koster, eds., pp. 13–21, Eurage, Amsterdam.Google Scholar
  16. Lunec, J., Halloran, S. P., White, A. G., and Dormandy, T. L., 1981, Free radical oxidation products in serum and synovial fluid in rheumatoid arthritis, J.Rheumatol., 8:233.PubMedGoogle Scholar
  17. Lunec, J., Blake, D. R., and McCleary, S. J., 1985, Self-perpetuating mechanisms of immunoglobulin G aggregation in rheumatoid inflammation, J.Clin.Invest., 76:2084.PubMedCrossRefGoogle Scholar
  18. Lunec, J., Wakefield, A., Brailsford, S., and Blake, D. R., 1986, Free radical altered IgG and its interaction with rheumatoid factor, in: “Free Radicals, Cell Damage and Disease,” C. Rice-Evans, ed., pp. 241–261, Richelieu Press, London.Google Scholar
  19. Lunec, J., Griffiths, H. R., Jones, A. F., and Blake, D. R., 1987, Protein fluorescence and its relationship to free radical activity, in: “Free Radicals, Oxidant Stress and Drug Action,” C. Rice-Evans, ed., pp. 151–167, Richelieu Press, London.Google Scholar
  20. Myers, C. E., McGuire, W. P., Liss, R. H., Ifrim, I., Grotzinger, K., and Young, R. C, 1977, Adriamycin: The role of lipid peroxidation in cardiac toxicity and tumor response, Science, 197:165.PubMedCrossRefGoogle Scholar
  21. O’Brien, P., 1969, Intracellular mechanisms for the decomposition of a lipid peroxide I. Decomposition by metal ions, haem compounds and nucleophiles, Can.J.Biochem., 47:485.PubMedCrossRefGoogle Scholar
  22. Rice-Evans, C., 1987, Oxidative modifications in erythrocytes induced by iron, in: “Free Radicals, Oxidant Stress and Drug Action,” C. Rice-Evans, ed., p. 307–330, Richelieu Press, London.Google Scholar
  23. Rice-Evans, C. and Baysal, E., 1987, Iron-mediated oxidative stress in erythrocytes, Biochem.J., 244:191.PubMedGoogle Scholar
  24. Rice-Evans, Omorphos, S. C., and Baysal, E., 1986a, Sickle cell membranes and oxidative damage, Biochem. J., 237:265.PubMedGoogle Scholar
  25. Rice-Evans, Omorphos, S. C., and Baysal, E., 1986b, Sickle cell pathology: Is the membrane important?, in : “Free Radicals, Cell Damage and Disease,” C. Rice-Evans, ed., pp. 149–166, Richelieu Press, London.Google Scholar
  26. Roshchupkin, D. I., Talitsky, V. V., and Peleritsyn, A. B., 1979, Fluorescence study of tryptophan photolysis, Photochem.Photobiol., 30:635.CrossRefGoogle Scholar
  27. Sies, H., 1986, Biochemistry of Oxidative Stress, Angewandte Chemi, 25:1058.CrossRefGoogle Scholar
  28. Singh, A., Koroll, G. W., and Cundall, R. B., 1982, Pulse radiolysis of aqueous solutions of sodium azide: Reaction of azide radical tryptophan and tyrosine, Radiat.Phys.Chem., 19:137.Google Scholar
  29. Slater, T. F., 1984, Free radical mechanisms in tissue injury, Biochem.J., 222:1.PubMedGoogle Scholar
  30. Slater, R. F., Benedetto, C., Cheeseman, K. H., Collins, M., Davies, M. J., and Flatman, S., 1986, Free radical and prostaglandin disturbances in cancer, in : “Free radicals, Cell Damage and Disease,” C. Rice-Evans, ed., pp. 57–72, Richelieu Press, London.Google Scholar
  31. Snyder, R., Parke, D. V., Kocsis, J. J., Jollow, D. J., Gibson, G. G. and Witmer, C. M., 1982, “Biological Reactive Intermediates,” Plenum Press.Google Scholar
  32. Tappel, A. L., 1980, Measurement of and protection from in vivo lipid peroxidation, in: “Free Radical Biology,” W. A. Pryor, ed., Vol. IV, pp. 1–45, Academic Press, New York.Google Scholar
  33. Tappel, A. L., and Dillard, C. J., 1981, In vivo lipid peroxidation: Measurement via exhaled pentane and protection by vitamin E, Fed.Proc. 40:174.PubMedGoogle Scholar
  34. Verweij, H., Christianse, K., and van Steveninck, J., 1982, Ozone-induced formation of 0,0-dityrosine cross-linked in proteins, Biochirn. Biophys.Acta., 701:180.CrossRefGoogle Scholar
  35. Wolff, S. P., and Dean, R. T., 1986, Framentation of proteins by free radicals and the effect on their susceptibility to enzyme hydrolysis, Biochem.J., 234:399.PubMedGoogle Scholar
  36. Wolff, S. P., Garner, A., and Dean, R. T., 1986, Free radicals, lipids and protein degradation, Trends Biochem.Sci., 11:27.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Catherine Rice-Evans
    • 1
  1. 1.Department of BiochemistryRoyal Free Hospital School of MedicineLondonUK

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