The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro

Oxidation of low density lipoprotein (LDL) is implicated in the development of atherosclerosis and dietary antioxidants may provide a useful therapy i n the prevention of LDL oxidation and atheroma development. The aim of thes e experiments was to investigate the antioxidant activity of the soybean is oflavone, genistein, in in vitro models of LDL oxidation. Genistein inhibit ed copper-mediated oxidation of LDL in a concentration-dependent manner by lengthening the time for conjugated diene formation (54.1 +/- 5.1 min in co ntrol LDL and 107.1 +/- 1.8 min with 5 mu mol/l genistein, P < 0.001) and d ecreasing the oxidation rate (14.4+/-1.9 nmol conjugated diene/mg LDL prote in/min in control LDL and 7.4+/-1.1 nmol conjugated diene/mg LDL protein/mi n with 5 mu mol/l genistein, P < 0.001), Peroxy radical (azo-initiated) oxi dation of LDL was significantly inhibited by 200 mu mol/l genistein as indi cated by: (i) increase in the time required for malondialdehyde (MDA) forma tion (7 h incubation compared to 3 h incubation with control LDL), (ii) 32, 44 and 46% decreases in MDA concentration compared to control samples foll owing 3, 4 and 5 h incubation, respectively and (iii) decrease in relative electrophoretic mobility (REM) of LDL. Incorporation of genistein into LDL and its resultant antioxidant activity was also investigated. LDL was isola ted from plasma which had been pre-incubated with 25, 50 or 100 mu mol/l ge nistein at 37 degrees C for 24 h. Approximately 3-4% of genistein present i n plasma was incorporated into LDL, however copper-mediated oxidation of co ntrol LDL and LDL isolated from plasma pre-incubated with genistein was not significantly different. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.