Biological Activities and Clinical Potential of Ebselen

  • Michael J. Parnham
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 264)

Abstract

Ebselen (2-pheny1–1,2-benzisoselenazol-3(2H)-one; Fig. 1) is a seleno-organic compound which exhibits catalytic GSH-dependent, hydroperoxide reducing properties, similar to the action of glutathione peroxidase (GSH-Px)1–3.

Keywords

Hepatitis Glutathione Mold Selenium Doxorubicin 

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References

  1. 1.
    A. Müller, E. Cadenas, P. Graf, and H. Sies, A novel biologically active seleno-organic compound I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen), Biochem. Pharmacol. 33:3235 (1984).PubMedGoogle Scholar
  2. 2.
    A. Wendel, M. Fausel, H. Safayhi, G. Tiegs, and R. Otter, A novel biologically active seleno-organic compound II. Activity of PZ 51 in relation to glutathione peroxidase,Biochem. Pharmacol.33:3241 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    H. Fischer and N. Dereu, Mechanism of the catalytic reduction of hydroperoxides by ebselen: A selenium-77 NMR study, Bull. Soc. Chim. Belg. 96:757 (1987).CrossRefGoogle Scholar
  4. 4.
    M. Maiorino, A. Roveri, M. Coassin, and F. Ursini, Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ 51), Biochem. Pharmacol. 37:2267 (1988).Google Scholar
  5. 5.
    M.J. Parnham and S. Kindt, A novel biologically active seleno-organic compound III. Effects of PZ 51 (Ebselen) on glutathione peroxidase and secretory activities of mouse macrophages, Biochem. Pharmacol. 33:3247 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    H. Safayhi, G. Tiegs, and A. Wendel, A novel biologically active seleno-organic compound V. Inhibition by ebselen (PZ 51) of rat peritoneal neutrophil lipoxygenase, Biochem. Pharmacol. 34:2691 (1985)PubMedCrossRefGoogle Scholar
  7. 7.
    P. Kuhl, H.O. Borbe, H. Fischer, A. Römer, and H. Safayhi, Ebselen reduces the formation of LTB¿ in human and porcine leukocytes by isomerisation to its 5S,12R-6-trans-isomer,Prostaglandins31:1029 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    A. Müller, H. Gabriel, and H. Sies, A novel biologically active seleno-organic compound IV. Protective glutathione-dependent effect of PZ 51 (ebselen) against ADP-Fe induced lipid peroxidation in isolated hepatocytes, Biochem. Pharmacol. 34:1185 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Hayashi and T.F. Slater, Inhibitory effects of ebselen on lipid peroxidation in rat liver microsomes,Free Rad. Res. Commun.2:179 (1986).Google Scholar
  10. 10.
    J.H. Doroshow, Prevention of doxorubicin-induced killing of MCF-7 human breast cancer cells by oxygen radical scavengers and iron chelating agents, Biochem. Biophys. Res. Commun. 135:330 (1986).CrossRefGoogle Scholar
  11. 11.
    W. Englberger, and M.J. Parnham, Inhibition by ebselen of macrophage eicosanoid generation and lymphocyte proliferation in vitro, Br. J. Pharmacol. 87:15P (1986).Google Scholar
  12. 12.
    S. Ichikawa, K. Omura, T. Katayama, N. Okamura, T. Ohtsuka, S. Ishibashi, and H. Masayasu, Inhibition of Superoxide anion production in guinea pig polymorphomuclear leukocytes by a seleno-organic compound, ebselen, J. Pharmacobio-Dyn. 10:595 (1987).CrossRefGoogle Scholar
  13. 13.
    M.J. Parnham, S. Leyck, N. Dereu, J. Winkelmann, and E. Graf, Ebselen (PZ 51): A GSH-peroxidase-like organoselenium compound with anti-inflammatory activity, Adv. Infl am. Res. 10:397 (1985).Google Scholar
  14. 14.
    M.J. Parnham, S. Leyck, P. Kuhl, J. Schalkwijk, and W.B. van den Berg, Ebselen: a new approach to the inhibition of peroxide dependent inflammation, Int. J. Tissue React. 9:45 (1987).PubMedGoogle Scholar
  15. 15.
    J. Schalkwijk, W.B. van den Berg, L.B.A. van de Putte, and L.A.B. Joosten, An experimental model for hydrogen peroxide-induced tissue damage. Effects of a single inflammatory mediator on (peri)articular tissues, Arthr. Rheum. 29:532 (1986).CrossRefGoogle Scholar
  16. 16.
    T.E. Van Dyke, L. Braswell, and S. Offenbacher, Inhibition of gingivitis by topical application of ebselen and rosmarinic acid, Agents and Actions 19: 376 (1986).CrossRefGoogle Scholar
  17. 17.
    I.A. Cotgreave, U. Johansson, G. Westergren, P.W. Moldéus, and R. Brattsand, The anti-inflammatory activity of ebselen but not thiols in experimental alveolitis and bronchiolitis, Agents and Actions 24: 313 (1988).PubMedCrossRefGoogle Scholar
  18. 18.
    D.R. Blake, R.E. Allen, and J. Lunec, Free radicals in biological systems -a review orientated to inflammatory processes, Br. Med. Bull. 43:371 (1987).Google Scholar
  19. 19.
    H.P. Härtung, B. Schäfer, K. Heininger, and K.V. Toyka, Interference with arachidonic acid metabolism suppresses experimental aller gic neuritis, Ann. Neurol. 20:168 (1986).Google Scholar
  20. 20.
    S. Ueda, T. Yoshikawa, H. Oyamada, T. Takemura, Y. Morita, N. Yoshida, S. Sugino, and M. Kondo, Effects of ebselen on acute gastric mucosal injury in rats, in: Abstracts, International Conference on Medical, Biochemical and Chemical Aspects of Free Radicals, p 228, Kyoto (1988).Google Scholar
  21. 21.
    K. Sakuma, H. Masayasu, H. Shibata, and S. Ashida, Ebselen, a seleno-organic compound, inhibits leukocyte aggregation and leukotriene B4 production in human and rats, in: Abstracts 4th International Symposium in Selenium in Biology and Medicine, p88, Univ. of Tübingen (1988).Google Scholar
  22. 22.
    A. Wendel, and G. Tiegs, A novel biologically active seleno-organic compound VI. Protection by ebselen (PZ 51) against galactosamine/endotoxin-induced hepatitis in mice,Biochem. Pharmac.35:2115 (1986).CrossRefGoogle Scholar
  23. 23.
    A. Wendel, G. Tiegs, C. Werner, and N. Dereu, Interaction of ebselen with hepatic arachidonate metabolism in vivo, Phosphorus and Sulphur 38:59 (1988).Google Scholar
  24. 24.
    M. Akasaki, T. Ikeda, F. Numata, Y. Kurebayashi, and W. Tsukada, Effect of ebselen (PZ 51) in liver failure induced by Propionobacterium acnes (P.acnes), in: Abstracts, 4th International Symposium on Selenium in Biology and Medicine., p 3, Univ. of Tübingen (1988).Google Scholar
  25. 25.
    T. Hashizume, S. Ide, and Y. Shimoto, Effect of ebselen (PZ 51) on experimental liver injury models, in: Abstracts, 4th International Symposium on Selenium in Biology and Medicine., p 38, Univ. of Tübingen (1988).Google Scholar
  26. 26.
    W. Hagmann, and D. Keppler, Leukotrienes and other eicosanoids in liver pathophysiology, in: The Liver: Biology and Pathobiology2nd Ed. I.M. Arias, W.B. Jakoby, H. Popper, D. Schachter, and D.A. Schafritz, ed., Raven Press, New York, p 793 (1988).Google Scholar
  27. 27.
    J. Tanaka, and F. Yamada, Ebselen (PZ 51) inhibits the formation of ischemic brain edema, in: Abstracts, 4th International Symposium on Selenium in Biology and Medicine., p 38, Univ. of Tübingen (1988).Google Scholar
  28. 28.
    L.D. Koller, and J.H. Exon, The two faces of selenium -deficiency and toxicity -are similar in animals and man, Can. J. Vet. Res. 50:297 (1986).Google Scholar
  29. 29.
    A. Müller, H. Gabriel, H. Sies, R. Terlinden, H. Fischer, and A. Römer, A novel biologically active selenoorganic compound VII. Biotransformation of ebselen in perfused rat liver, Biochem. Pharmacol. 37:1103 (1988).Google Scholar
  30. 30.
    R. Terlinden, M. Feige, and A. Römer, Determination of the two major metabolites of ebselen in human plasma by high-performance liquid chromatography, J. Chromatography 430:438 (1988).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Michael J. Parnham
    • 1
  1. 1.Cologne Research CentreRhône-Poulenc/NattermannCologne 30Germany

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