title: A novel biologically active seleno-organic compound--V. Inhibition by ebselen (PZ 51) of rat peritoneal neutrophil lipoxygenase.
abstract: Suspensions of rat peritoneal PMNLs elicited with glycogen were stimulated by calcium and an ionophore to produce leukotrienes from endogenous arachidonic acid. We investigated the effect of the non-toxic, anti-inflammatory seleno-organic compound, ebselen (PZ 51). When ethanolic extracts of the medium of stimulated cells were analysed by HPLC, a dose-dependent inhibition by ebselen of LTB4 formation with a concomitant decrease of 5-HETE production was found. Half-maximum inhibition was observed at 20 mumoles/l ebselen. Similar findings were obtained after analysis of chloroform extracts of both cells and medium using a different HPLC system. Under these conditions, enhanced 5-HETE formation was associated with reduced production of LTB4 and other di-HETE isomers, when purified glutathione peroxidase + GSH were present. We conclude that the reported GSH peroxidase-like activity of ebselen, catalysing the reduction of 5-HPETE to 5-HETE, can not account for our findings. Therefore, the lipoxygenase reaction itself apparently represents the site of inhibition of LTB4 formation by ebselen.
authors.forename: H
authors.initials: H
authors.lastname: Safayhi
authors.forename: G
authors.initials: G
authors.lastname: Tiegs
authors.forename: A
authors.initials: A
authors.lastname: Wendel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D054833:Isoindoles; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D016566:Organoselenium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D001393:Azoles; D006893:Hydroxyeicosatetraenoic Acids; D054833:Isoindoles; D016859:Lipoxygenase Inhibitors; D016566:Organoselenium Compounds; D007975:Leukotriene B4; C042986:ebselen; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D005979:Glutathione Peroxidase; D012643:Selenium