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Inhibition of superoxide and nitric oxide release and protection from reoxygenation injury by ebselen in rat kupffer cells
Author(s) -
Wang JiFeng,
Komarov Pavel,
Sies Helmut,
de Groot Herbert
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840150623
Subject(s) - ebselen , nitric oxide , chemistry , superoxide , nadph oxidase , pharmacology , nitric oxide synthase , biochemistry , kupffer cell , ic50 , reactive oxygen species , catalase , antioxidant , medicine , in vitro , biology , glutathione peroxidase , enzyme , organic chemistry
Luminol chemiluminescence in phorbolesteractivated cultured rat liver Kupffer cells was strongly inhibited by the selenoorganic compound ebselen (IC 50 = 2 μmol/L). Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3[2H]one) also diminished reduction of ferricytochrome c (IC 50 = 10μmol/L), indicating a suppression of superoxide anion formation. Likewise, in lipopolysaccharide‐pretreated Kupffer cells, ebselen proved to be a potent inhibitor of the conversion of oxyhemoglobin to methemoglobin (IC 50 = 3 μmol/L) as a measure of nitric oxide formation. The sulfurcontaining analog (2‐phenyl‐1,2‐benzisothiazol‐3[2H]one) and the ebselen derivative, methylselenobenzanilide, were inactive. These results indicate that ebselen is a potent inhibitor of NADPH oxidase in Kupffer cells, as has been reported for other macrophages and granulocytes. In addition, they suggest a novel characteristic of ebselen, namely very effective inhibition of nitric oxide synthase of macrophages. In line with its inhibitory effects on the release of reactive oxygen species by macrophages, complemented by its antioxidant properties, ebselen was potent in the prevention of reoxygenation injury of Kupffer cells (IC 50 ∼ 5 μmol/L). (H EPATOLOGY 1992;15:1112–1116).