MOLECULAR ACTIONS OF EBSELEN - AN ANTIINFLAMMATORY ANTIOXIDANT

1. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a non-toxic se leno-organic drug with antiinflammatory, antiatherosclerotic and cytop rotective properties. 2. Ebselen and some of its metabolites are effec tive reductants of hydroperoxides including those arising in biomembra nes and lipoproteins. 3. By reactions with hydroperoxides and thiols s everal interconversion cycles are formed which include ebselen metabol ites with varying oxidation number of the selenium. 4. In the presence of thiols ebselen mimics the catalytic activities of phospholipid hyd roperoxide glutathione peroxidase. 5. Ebselen inhibits at low concentr ations a number of enzymes involved in inflammation such as lipoxygena ses, NO synthases, NADPH, oxidase, protein kinase C and H+/K+-ATPase. The inhibitions are manifested on the cellular level and may contribut e to the antiinflammatory potential of ebselen.