Ebselen, a Seleno-Organic Compound, Inhibits Leukocyte Aggregation and Reduces the Plasma Leukotriene B4 Level in Humans and Rats

  • K. Sakuma
  • H. Masayasu
  • H. Shibata
  • S. Ashida

Abstract

Recent evidence suggests that intravascular activation of leukocytes may be implicated in the pathogenesis of inflammation, postischemic injury and atherothrombotic diseases (Harlan 1985). Thus, the prevention of leukocyte activation represents a possible target for therapeutic intervention in these diseases. Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] is a seleno-organic compound which catalyzes the degradation of hydroperoxides (Müller et al. 1984), converts leukotriene B4 (LTB4) into its biologically inactive 6-trans isomer (Kuhl et al. 1986) in the presence of glutathione, and inhibits arachidonate 5-lipoxygenase (Safayhi et al. 1985) and superoxide anion production (Ichikawa et al. 1987) in leukocytes. We have, therefore, studied the effect of ebselen on leukocyte activation in rats and humans after oral administration. This was done by assessing its inhibition of LTB4-induced whole blood aggregation ex vivo. In addition, we have investigated possible effects of ebselen on platelet aggregation and the concentrations of LTB4, thromboxane B (TXB2) and 6-keto-prostaglandin F a (6-keto-PGF1 α) in plasma after oral administration.

Keywords

Placebo Peroxide Attenuation Glutathione Citrate 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • K. Sakuma
    • 1
  • H. Masayasu
    • 1
  • H. Shibata
    • 2
  • S. Ashida
    • 1
  1. 1.Research InstituteDaiichi Seiyaku Co. Ltd.Edogawa-ku, Tokyo 134Japan
  2. 2.Department of Internal MedicineKitasato University School of MedicineKitasato, Sagamihara-shi, Kanagawa 228Japan

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