title: Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells.
abstract: The effects of the flavonoid silibinin, which is used for the treatment of liver diseases, on the formation of reactive oxygen species and eicosanoids by human platelets, white blood and endothelial cells were studied. Silibinin proved to be a strong scavenger of HOCI (IC50 7 microM), but not of O2- (IC50 > 200 microM) produced by human granulocytes. The formation of leukotrienes via the 5-lipoxygenase pathway was strongly inhibited. In human granulocytes IC50-values of 15 microM and 14.5 microM silibinin were detected for LTB4 and LTC4/D4/E4/F4 formation, respectively. In contrast to this, three- to fourfold silibinin concentrations were necessary to half maximally inhibit the cyclooxygenase pathway. For PGE2 formation by human monocytes an IC50-value of 45 microM silibinin was found. IC50-values of 69 microM and 52 microM silibinin were determined for the inhibition of TXB2 formation by human thrombocytes and of 6-K-PGF1 alpha formation by human omentum endothelial cells, respectively. Thus, the deleterious effects of HOCI that can lead to cell death, and those of leukotrienes that are especially important in inflammatory reactions, can be inhibited by silibinin in concentrations that are reached in vivo after the usual clinical dose. Silibinin is thought not only to display hepatoprotective properties but might also be cytoprotective in other organs and tissues.
authors.affiliation: Institut für Physiologische Chemie, Universitätsklinikum, Essen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Dehmlow
authors.forename: N
authors.initials: N
authors.lastname: Murawski
authors.forename: H
authors.initials: H
authors.lastname: de Groot
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis; D008163:Luminescent Measurements; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012838:Silymarin / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D016166:Free Radical Scavengers; D015289:Leukotrienes; D017382:Reactive Oxygen Species; D012838:Silymarin; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D006997:Hypochlorous Acid; D015232:Dinoprostone