Future trends in free radical studies

  • W. Huber
Part of the Inflammation: Mechanisms and Treatment book series (FTIN, volume 4)


Free radical mediated events in vivo, particularly as related to inflammation, have been and are likely to remain for the foreseeable future intimately wedded to the active species derived from molecular oxygen, or, as it is more properly called, dioxygen. Since the discovery of the superoxide dismutating activity of metalloprotein enzymes (SOD) having copper, manganese or iron at their active site, and that of the selenium containing glutathione peroxidase, these ubiquitously occurring endogenous enzymes and the active species they regulate have been the subject of a veritable landslide of investigations1-5. To properly assess future trends at this juncture, I think it is important to have a brief look first at ‘what is what’ in our present knowledge of this Janus-faced role of oxygen centred free radicals in tissue.


Superoxide Dismutase Glutathione Peroxidase Oxygen Free Radical Duchenne Muscular Dystrophy Chronic Cystitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bors, W., Saran, M., Lengfelder, E., Spötte, R. and Michel, C. (1974). The relevance of the superoxide anion radical in biological systems. Curr. Top. Radia. Res. Q., 9, 247Google Scholar
  2. 2.
    Fee, J. A. and Valentine, J. S. (1977). Chemical and physical properties of superoxide. In Michelson, A. M., McCord, J. M. and Fridovich, I. (eds.), Superoxide and Superoxide Dismutases, pp. 19–60. (London: Academic Press)Google Scholar
  3. 3.
    Willson, R. L. (1979). Hydroxyl radicals and biological damage in vitro: What relevance in vivo? In Oxygen Free Radicals and Tissue Damage. Ciba Symp. 65, new series, pp. 19–42. (Amsterdam: Excerpta Medica)Google Scholar
  4. 4.
    Fridovich, I. (1976). Superoxide dismutase and the chemistry of hydrogen peroxide. In Pryor, W. A. (ed.) Free Radicals in Biology, Vol. I pp. 239–277. (New York: Academic Press)Google Scholar
  5. 5.
    Flohé, L. (1979). Glutathione peroxidase: fact and fiction. In Oxygen Free Radicals and Tissue Damage. Ciba Symp. 65, new series, pp. 95–122. (Amsterdam: Excerpta Medica)Google Scholar
  6. 6.
    Haber, F. and Willstätter, R. (1931). Unpaarigkeit und Radikalketten in Reaktionsmechanismus organischer und enzymatischer Vorgänge. Chem. Berichte, 64, 2844Google Scholar
  7. 7.
    Gerschman, R., Gilbert, D. L., Nye, S.W., Dwyer, P. and Fenn, W.O. (1954). Oxygen poisoning and x-irradiation. A mechanism in common. Science, 119, 623PubMedCrossRefGoogle Scholar
  8. 8.
    Czapski, G. (1971). Superoxide anion: pulse radiolysis in frozen solutions. Ann. Rev. Phys. Chem., 22, 171CrossRefGoogle Scholar
  9. 9.
    Fridovich, I. and Handler, P. (1958). Xanthine oxidase III. Sulfite oxidation as an ultrasensitive assay. J. Biol. Chem., 233, 1578PubMedGoogle Scholar
  10. 10.
    Mills, G. C. (1957). Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown. J. Biol. Chem., 229, 189PubMedGoogle Scholar
  11. 11.
    Sies, H. (1974). Biochemistry of the peroxisome in the liver cell. Angew. Chem. Int. Ed. Engl., 13, 706PubMedCrossRefGoogle Scholar
  12. 12.
    Mann, T. and Keilin, D. (1939). Hemocuprein and hepatocuprein. Proc. R. Soc. London, Ser. B, 126, 303CrossRefGoogle Scholar
  13. 13.
    Huber, W., Schulte, T. L., Carson, S., Goldhamer, R. E. and Vogin, E.E. (1968). Some chemical and pharmacological properties of a novel antiinflammatory protein. Toxicol. Appl. Pharmacol., 12, 308Google Scholar
  14. 14.
    McCord, J. M. and Fridovich, I. (1969). Superoxide dismutase. An enzymic function for erythrocuprein (Hemocuprein). J. Biol. Chem., 244, 6049PubMedGoogle Scholar
  15. 15.
    Steinman, H.M. and Hill, R. L. (1973). Sequence homologies among bacterial and mitochondrial superoxide dismutases. Proc. Natl. Acad. Sci. (USA), 70, 3725CrossRefGoogle Scholar
  16. 16.
    Weisiger, R. A. and Fridovich, I. (1973). Superoxide dismutase: Organelle specificity. J. Biol. Chem., 248, 3582PubMedGoogle Scholar
  17. 17.
    Menander-Huber, K. B. (1979). Double-blind controlled clinical trials in man with bovine Cu-Zn superoxide dismutase (orgotein). In Bannister, W. H. and Bannister, J. V. (eds.) The Significance of Superoxide and Superoxide Dismutase. Vol. II: Biological and Clinical Aspects. (New York: Elsevier in press)Google Scholar
  18. 18.
    Johnston, R.B. Jr., Keele, B. B. Jr., Misra, H.P., Webb, L. S., Lehmeyer, J. E. and Rajagopalan, K. V. (1975). Superoxide anion generation and phagocytic bactericidal activity. In Bellanti, J. A. and Dayton, D. H. (eds.) The Phagocytic Cell in Host Resistance, pp. 61–75. (New York: Raven Press)Google Scholar
  19. 19.
    Roos, D. and Weening, R. S. (1979). Defects in the oxidative killing of microorganisms by phagocytic leukocytes. In Oxygen Free Radicals and Tissue Damage. Ciba Symp. 65, new series, pp. 225–262. (Amsterdam: Excerpta Medica)Google Scholar
  20. 20.
    Badwey, J.A. and Karnovsky, M. L. (1979). Production of superoxide and hydrogen peroxide by an N ADH-oxidase in guinea pig polymorphonuclear leukocytes. J. Biol. Chem., 254, 11530PubMedGoogle Scholar
  21. 21.
    Klebanoff, S. J. and Rosen, H. (1979). The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes. In Oxygen Free Radicals and Tissue Damage. Ciba Symp. 65, new series, 262–283. (Amsterdam: Excerpta Medica)Google Scholar
  22. 22.
    Babior, B. M. and Kipnes, R. S. (1977). Superoxide-forming enzyme from human neutrophils: evidence for a flavin requirement. Blood, 50, 517PubMedGoogle Scholar
  23. 23.
    McCord, J. M. and Salin, M. L. (1977) Self-directed cytotoxicity of phagocyte-generated superoxide free radical. In Rossi, F., Patriarca, P. L. and Romeo, D. (eds.) Movement, Metabolism, and Bactericidal Mechanisms of Phagocytes, pp. 257–264. (Padua: Piccin)Google Scholar
  24. 24.
    McCord, J. M. (1974). Free radicals and inflammation: protection of synovial fluid by superoxide dismutase. Science, 185, 529PubMedCrossRefGoogle Scholar
  25. 25.
    Huber, W. and Saifer, M. G. P. (1977). Orgotein, the drug version of bovine Cu-Zn superoxide dismutase. I. A summary account of safety and pharmacology in laboratory animals. In Michelson, A. M., McCord, J. M. and Fridovich, I. (eds.) Superoxide and Superoxide Dismutases pp. 517–536. (New York: Academic Press)Google Scholar
  26. 26.
    Huber, W., Menander-Huber, K. B., Saifer, M. G. P. and Williams, L. D. (1979). Bioavailability of superoxide dismutase: Implications for the anti-inflammatory action mechanism of orgotein. Agents Actions Suppl. (In press)Google Scholar
  27. 27.
    Menander-Huber, K. B. and Huber, W. (1977). Orgotein, the drug version of bovine Cu-Zn superoxide dismutase. II. A summary account of clinical trials in man and animals. In Michelson, A. M., McCord, J.M. and Fridovich, I. (eds.) Superoxide and Superoxide Dismutases, pp. 537–549. (New York: Academic Press)Google Scholar
  28. 28.
    Huber, W. (1979). Orgotein (bovine Cu-Zn superoxide dismutase) an anti-inflammatory protein drug: Discovery, toxicology and pharmacology. Eur. J. Rheumatol. Suppl. (In press)Google Scholar
  29. 29.
    Hili, H. A.O. (1979). The identity of superoxide radical anion species. In Oxygen Free Radicals and Tissue Damage Ciba Symp. 65, new series, pp. 363–366. (Amsterdam: Excerpta Medica)Google Scholar
  30. 30.
    Tanford, C. (1961). Physical Chemistry of Macromolecules. p. 317. (New York: Wiley).Google Scholar
  31. 31.
    Fridovich, I. (1979). Superoxide dismutases: Defense against endogenous superoxide radical. In Oxygen Free Radicals and Tissue Damage. Ciba Symp. 65, new series pp. 77–93. (Amsterdam: Excerpta Medica)Google Scholar
  32. 32.
    Niehaus, W. G. (1978). A proposed role of superoxide anion as a biological nucleophile in the deesterification of phospholipids. Bioorg. Chem., 7, 77CrossRefGoogle Scholar
  33. 33.
    Fee, J. A. (1979). On the question of superoxide toxicity and the biological function of superoxide dismutases. In Third International Symposium on Oxidases and Related Oxidation-Reduction Systems. (Albany: New York)Google Scholar
  34. 34.
    Ichihara, K., Kuzonose, E., Kuzonose, M. and Mori, T. (1977). Manganese superoxide dismutase content of mycobacterium lepramurium. J. Biochem., 81, 1427PubMedGoogle Scholar
  35. 35.
    Giannopolitis, C. N. and Ries, J. K. (1977). Cu-Zn superoxide dismutases content of seedlings of corn, peas and oats. Plant Physiol., 59, 309PubMedCrossRefGoogle Scholar
  36. 36.
    Schrauzer, G.N., White, D. A. and Schneider, C.J. (1977). Cancer mortality correlation studies. III. Statistical associations with dietary selenium intakes. Bioinorg. Chem., 7, 23PubMedCrossRefGoogle Scholar
  37. 37.
    Huber, W., Saifer, M. G. P. and Williams, L. D. (1979). Superoxide dismutase pharmacology and orgotein efficacy: New perspectives. In Bannister, W. H. and Bannister, J. V. (eds.) The Significance of Superoxide and Superoxide Dismutase. Vol. II: Biological and Clinical Aspects. (New York: Elsevier, in press)Google Scholar
  38. 38.
    Ward, P. A. (1974). Personal communicationGoogle Scholar
  39. 39.
    Smith, L. L., Rose, M.S. and Wyatt, I. (1979). The pathology and biochemistry of paraquat. In Oxygen Free Radicals and Tissue Damage. Ciba Symp. 65, new series, pp. 321–341. (Amsterdam: Excerpta Medica)Google Scholar
  40. 40.
    Autor, A-P. (1974). Reduction of paraquat toxicity by superoxide dismutase. Life Sci., 14, 1309PubMedCrossRefGoogle Scholar
  41. 41.
    Huber, W. and Menander-Huber, K. B. (1979). Unpublished observationsGoogle Scholar
  42. 42.
    Lown, J. W. and Sim, S. (1977). The mechanism of the bleomycin-induced cleavage of DNA. Biochem. Biophys. Res. Commun., 77, 1150PubMedCrossRefGoogle Scholar
  43. 43.
    Goodman, J. and Hochstein, P. (1977). Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochem. Biophys. Res. Commun., 77, 797PubMedCrossRefGoogle Scholar
  44. 44.
    McGinness, J. E., Proctor, P. H., Demopoulos, H. B., Hokanson, J. A. and Kirkpatrick, D. S. (1978). Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase). Physiol. Chem. Phys., 10, 267PubMedGoogle Scholar
  45. 45.
    Edsmyr, F., Huber, W. and Menander, K. B. (1976). Orgotein efficacy in ameliorating side effects due to radiation therapy. I. Double-blind, placebo-controlled trial in patients with bladder tumors. Curr. Ther. Res., Clin. Exp., 19, 198Google Scholar
  46. 46.
    Williams, L. D., Dang, P. H. C., Gerstl, B. and Huber, W. (1979). Unpublished resultsGoogle Scholar
  47. 47.
    Harman, D. (1956). Ageing: A theory based on free radical and radiation chemistry. J. Gerontol., 11, 298PubMedGoogle Scholar
  48. 48.
    Fridovich, I. (1977). Oxygen is toxic! Bioscience, 27, 462CrossRefGoogle Scholar
  49. 49.
    Menander-Huber, K. B., Huskisson, E. C. and Huber, W. (1978). Inflammatory osteoarthritis as an in vivo model disease in man for the evaluation of anti-inflammatory drugs. In International Congress of Inflammation. (Bologna: Italy, Oct 31-Nov 3) Abstract P2/44Google Scholar

Copyright information

© MTP Press Limited 1980

Authors and Affiliations

  • W. Huber
    • 1
  1. 1.USA

Personalised recommendations