Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein

Hyperglycemia has been assumed to be responsible for oxidative stress in di abetes. In this respect, glucose autoxidation and advanced glycation end pr oducts (AGE) may play a causal role in the etiology of diabetic complicatio ns as e.g. atherosclerosis. There is now growing evidence that the oxidativ e modification of LDL plays a potential role in atherogenesis. Glucose deri ved oxidants have been shown to peroxidise LDL. In the present study, genis tein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxida tion radical products. Daidzein, (4', 7-dihydroxyisoflavone) an other phyto estrogen of soy, was tested in parallel. Genistein - in contrast to daidzei n - effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in el ectrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucos e-oxidized LDL to increase tissue factor (TF) synthesis in human endothelia l cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influenc e the nonenzymatic protein glycation reaction as measured by the in vitro f ormation of glycated LDL. As the protective effect of genistein on LDL athe rogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a so y diet in preventing chronic vascular diseases and early atherogenic events .