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

Abstract

Oxidation of low density lipoprotein (LDL) is implicated in the development of atherosclerosis and dietary antioxidants may provide a useful therapy in the prevention of LDL oxidation and atheroma development. The aim of these experiments was to investigate the antioxidant activity of the soybean isoflavone, genistein, in in vitro models of LDL oxidation. Genistein inhibited copper-mediated oxidation of LDL in a concentration-dependent manner by lengthening the time for conjugated diene formation (54.1±5.1 min in control LDL and 107.1±1.8 min with 5 μmol/l genistein, P<0.001) and decreasing the oxidation rate (14.4±1.9 nmol conjugated diene/mg LDL protein/min in control LDL and 7.4±1.1 nmol conjugated diene/mg LDL protein/min with 5 μmol/l genistein, P<0.001). Peroxy radical (azo-initiated) oxidation of LDL was significantly inhibited by 200 μmol/l genistein as indicated by: (i) increase in the time required for malondialdehyde (MDA) formation (7 h incubation compared to 3 h incubation with control LDL), (ii) 32, 44 and 46% decreases in MDA concentration compared to control samples following 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 isolated from plasma which had been pre-incubated with 25, 50 or 100 μmol/l genistein at 37°C for 24 h. Approximately 3–4% of genistein present in plasma was incorporated into LDL, however copper-mediated oxidation of control LDL and LDL isolated from plasma pre-incubated with genistein was not significantly different.