FREE-RADICAL SCAVENGING AND ANTIOXIDATIVE PROPERTIES OF SILIBIN COMPLEXES ON MICROSOMAL LIPID-PEROXIDATION

The antioxidant properties of silibin complexes, the water-soluble for m silibin dihemisuccinate (SDH), and the lipid-soluble form, silibin p hosphatidylcholine complex known as IdB 1016, were evaluated by studyi ng their abilities to react with the superoxide radical anion (O-2(-)) , and the hydroxyl radical (OH.). In addition, their effect on pulmona ry and hepatic microsomal lipid peroxidation had been investigated. Su peroxide radicals were generated by the PMS-NADH system and measured b y their ability to reduce NET. IC50 concentrations for the inhibition of the NET reduction by SDH and IdB 1016 were found to be 25 mu M and 316 mu M respectively. Both silibin complexes had an inhibitory effect on xanthine oxidase activity. SDH reacted rapidly with OH. radicals a t approximately diffusion controlled rate and the rate constant was fo und to be (K = 8.2 x 10(9) M(-1) s(-1)); it appeared to chelate Fe2+ i n solution. In hepatic microsomes, when lipid peroxidation was induced by Fe2+, SDH inhibited by 39.5 per cent and IdB 1016 by 19.5 per cent , whereas when lipid peroxidation was induced by CuOOH, IdB 1016 exert ed a better protective effect than SDH (29.4 per cent and 19.4 per cen t inhibition, respectively). In both microsomal systems lipid peroxida tion proceeded through a thiol depletion mechanism which could be rest ored in the presence of silibin complexes. Low levels of lipid peroxid ation in pulmonary microsomes point out the differences between in-vit ro lipid peroxidation occurring in microsomes of different tissues. Th e results support the free radical scavenger and antioxidative propert ies of silibin when it is complexed with a suitable molecule to increa se its bioavailability. ((C) 1997 by John Wiley & Sons, Ltd.)