Differential effect of ebselen on compound 48/80- and anti-IgE-induced histamine release from rat peritoneal mast cells.
2-Phenyl-1, 2-benzisoselenazol-3-(2H)one (ebselen), a nontoxic seleno-organic compound, exhibits anti-inflammatory activity through the inhibition of many enzymes involved in inflammation. In view of the role played by histamine in the pathophysiology of inflammation, we looked at the effect of ebselen on histamine secretion by rat peritoneal mast cells. It inhibited compound 48/80-induced histamine release in a concentration-dependent manner. Half-maximal and maximal (100%) inhibitory response occurred at 5.10(-7)M and 10(-5)M, respectively. In contrast, ebselen was without any effect on histamine release induced immunologically. Prevention of the inhibitory effect of ebselen by GSH suggests that it interacts with critical thiols involved in the compound 48/80 activation pathway.
Tchoumkeu-Nzouessa
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Ciba Vision Preclinical Ophtha Unit (Novartis), Basel, Switzerland. guizot.tchoumkeu@cibavision.novartis.com
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D054833:Isoindoles; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010529:Peritoneal Cavity; D051381:Rats; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000888:Antibodies, Anti-Idiotypic; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; C042986:ebselen