title: Inhibition of superoxide anion radical production by ebselen (PZ51) and its sulfur analogue (PZ25) in guinea pig alveolar macrophages.
abstract: The production of superoxide anion radicals by guinea pig alveolar macrophages is stimulated by the chemotactic peptide N-formylmethionyl-leucylphenylalanine and the protein kinase C activator phorbol-12-myristate-13-acetate. Both stimulations are completely and equipotently (IC50 = 20 microM) inhibited by the seleno-organic compound ebselen. As the sulfur containing analogue, which is devoid of glutathione peroxidase-like activity, shows the same inhibitory activity towards superoxide anion radical production the observed effect of ebselen can not be explained by the described glutathione peroxidase-like activity. The observed inhibition is probably caused by an inhibition of protein kinase C or inhibition at a level distal to protein kinase C activation.
authors.affiliation: Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Leurs
authors.forename: H
authors.initials: H
authors.lastname: Timmerman
authors.forename: A
authors.initials: A
authors.lastname: Bast
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D005609:Free Radicals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D054833:Isoindoles; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D016566:Organoselenium Compounds; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001393:Azoles; D005609:Free Radicals; D054833:Isoindoles; D016566:Organoselenium Compounds; D013844:Thiazoles; D013481:Superoxides; C060674:2-phenyl-1,2-benzisothiazol-3-(2H)-one; C042986:ebselen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012643:Selenium; D013755:Tetradecanoylphorbol Acetate