title: Studies on the anti-inflammatory activity of ebselen. Ebselen interferes with granulocyte oxidative burst by dual inhibition of NADPH oxidase and protein kinase C?
abstract: Ebselen (PZ51, 2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) was shown to be an inhibitor of human granulocyte oxidative burst stimulated by phorbol myristate acetate (IC50 25 microM). Estimation of the primary oxygen metabolites of the burst was complicated by the redox chemistry of Ebselen. Ebselen inhibited NADPH-stimulated superoxide generation by a partially purified NADPH oxidase preparation with an IC50 of 0.5-1.0 microM. Ebselen was also shown to inhibit the activity of partially purified Ca2+- and phospholipid-dependent protein kinase C (IC50 ca. 0.5 microM). Phorbol ester-stimulated phosphorylation of protein in intact cells was inhibited by Ebselen (IC50 ca. 50 microM). These pharmacodynamic properties of Ebselen are discussed in terms of its anti-inflammatory activity in vivo. The findings are also discussed in terms of Ebselen's known ability to interact with sulfhydryl components of cells, particularly critical thiol components of the enzymes studied.
authors.affiliation: Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I A
authors.initials: IA
authors.lastname: Cotgreave
authors.forename: S K
authors.initials: SK
authors.lastname: Duddy
authors.forename: G E
authors.initials: GE
authors.lastname: Kass
authors.forename: D
authors.initials: D
authors.lastname: Thompson
authors.forename: P
authors.initials: P
authors.lastname: Moldéus
mesh_terms: D001393:Azoles / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D054833:Isoindoles; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases; D016566:Organoselenium Compounds; D010101:Oxygen Consumption / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012643:Selenium / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D010750:Phosphoproteins; D013481:Superoxides; C042986:ebselen; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C; D012643:Selenium; D013755:Tetradecanoylphorbol Acetate