Inhibition of Superoxide Anion Radical Production by Ebselen (PZ51) and Its Sulfur Analogue (PZ25) in Guinea Pig Alveolar Macrophages

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.