Agents and Actions

, Volume 36, Issue 1–2, pp 107–111 | Cite as

The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation

  • H. R. Griffiths
  • E. J. Dowling
  • T. Sahinoglu
  • D. R. Blake
  • M. Parnham
  • J. Lunec
Inflammation and Immunomodulation


The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage).

The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.


Lipid Peroxide Lipid Peroxidation Experimental Model Oxidative Damage 
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  1. [1]
    J. Lunec and D. R. Blake,Oxygen radicals: Their relevance to disease processes. InThe Metabolic and Molecular Basis of Acquired Disease. (Eds. R. D. Cohen, K. G. M. Alberti, B. Lewis and A. M. Denman) pp. 189–212 Balliere Tindall, London 1990.Google Scholar
  2. [2]
    J. Lunec,Fluorescence: A marker of free radical damage induced in human gamma globulin. Biochem Soc. Proc.10, 12 (1980).Google Scholar
  3. [3]
    B. Halliwell, J. R. Hoult and D. R. Blake,Oxidants, inflammation and anti-inflammatory drugs. FASEB J.2, 2867–2873 (1985).Google Scholar
  4. [4]
    M. J. Parnham and E. Graf,Seleno-organic compounds and the therapy of hydroperoxide linked pathological conditions. Biochem. Pharmacol.36, 3095–3102 (1987).PubMedGoogle Scholar
  5. [5]
    J. Schaiwijk, W. B. Van Den Berg, L. B. A. Van de Putte and L. A. B. Joosten,An experimental model for H 2 O 2 induced tissue damage. Arthr. Rheum.29, 532–538.Google Scholar
  6. [6]
    E. J. Dowling, M. J. Parnham, C. J. Morris, A. Dabbagh and D. R. Blake,An experimental model of ROS-mediated endothelial cell damage. J. Leukoc. Biol.46, 336 (1989).Google Scholar
  7. [7]
    J. Stocks, J. M. C. Gutteridge, R. J. Sharp and T. L. Dormandy,The inhibition of lipid autooxidation by human serum and its relation to serum proteins and α tocopherol. Clin. Sci.47, 223–233 (1974).Google Scholar
  8. [8]
    H. R. Griffiths, J. Unsworth, D. R. Blake and J. Lunec,Oxidation of amino acids within serum proteins. In:Free Radicals: Chemistry, Biology and Medicine. (Eds. C. Rice Evans and T. L. Dormandy) pp. 439–454, Richelieu Press, 1988.Google Scholar
  9. [9]
    J. Lunec, D. R. Blake, S. J. McCleary, S. Brailsford and P. A. Bacon,Self perpetuating mechanisms of IgG aggregation in rheumatoid inflammation. J. Clin. Invest.76, 2085–2090 (1985).Google Scholar
  10. [10]
    H. R. Griffiths, J. Winkles, P. Emery and J. Lunec,Oxygen radical generation during inflammation: A potential cause of agalactosylation of IgG. Brit. J. Rheum. Suppl.228, 9 (1989).Google Scholar
  11. [11]
    H. R. Griffiths and J. Lunec,The effects of oxygen free radicals on the carbohydrate moiety of IgG. FEBS Letts.245, 95–99 (1989).Google Scholar
  12. [12]
    A. F. Jones and J. Lunec,Protein fluorescence and its relationship to free radical activity. Brit. J. Cancer55, (Suppl. VIII) 60–65 (1987).Google Scholar
  13. [13]
    R. B. Parekh, R. A. Dwek, B. J. Sutton et al.Association of rheumatoid arthritis and primary osteo arthritis with changes in the glycosylation status of total serum IgG. Nature316 (6027), 452–457 (1985).PubMedGoogle Scholar
  14. [14]
    J. S. Axford, L. Mackenzie and P. M. Lydyard,Reduced B cell galactosyl transferase activity in rheumatoid arthritis. Lancetii, 1486–1488 (1987).Google Scholar
  15. [15]
    R. Dube, G. A. W. Rook, J. Steele et al.,Agalactosylated IgG in inflammatory bowel disease: Correlation with CRP. Gut31, 431–434 (1990).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1992

Authors and Affiliations

  • H. R. Griffiths
    • 1
  • E. J. Dowling
    • 2
  • T. Sahinoglu
    • 2
  • D. R. Blake
    • 2
  • M. Parnham
    • 3
  • J. Lunec
    • 1
  1. 1.Molecular Toxicity Group, Clinical Sciences BlockGlenfield General HospitalLeicesterUK
  2. 2.Bone and Joint Research UnitThe London Hospital Medical CollegeLondonUK
  3. 3.A Nattermann & Cie, Pharmacology ResearchCologneGermany

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