SCAVENGING OF REACTIVE OXYGEN SPECIES AND INHIBITION OF ARACHIDONIC-ACID METABOLISM BY SILIBININ IN HUMAN-CELLS

The effects of the flavonoid silibinin, which is used for the treatmen t of liver diseases, on the formation of reactive oxygen species and e icosanoids by human platelets, white blood and endothelial cells were studied. Silibinin proved to be a strong scavenger of HOCl (IC50 7 mu M), but not of O-2(-) (IC50>200 mu M) produced by human granulocytes. The formation of leukotrienes via the 5-lipoxygenase pathway was stron gly inhibited. In human granulocytes IC50-values of 15 mu M and 14.5 m u M silibinin were detected for LTB(4) and LTC(4)/D-4/E(4)/F-4 formati on, respectively. In contrast to this, three- to fourfold silibinin co ncentrations were necessary to halfmaximally inhibit the cyclooxygenas e pathway. For PGE(2) formation by human monocytes an IC50-value of 45 mu M silibinin was found. IC50-values of 69 mu M and 52 mu M silibini n were determined for the inhibition of TXB(2) formation by human thro mbocytes and of 6-K-PGF(1 alpha) formation by human omentum endothelia l cells, respectively. Thus, the deleterious effects of HOCl that can lead to cell death, and those of leukotrienes that are especially impo rtant in inflammatory reactions, can be inhibited by silibinin in conc entrations that are reached in vivo after the usual clinical dose. Sil ibinin is thought not only to display hepatoprotective properties but might also be cytoprotective in other organs and tissues.