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

Abstract

Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, 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 autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Vascular targets of redox signalling in diabetes mellitus

“…Thus, stimulation of p125FAK by ROS mediates reversible changes in cell shape and morphology, reorganisation of the cytoskeleton and redistribution of cell-surface adhesion proteins [119]. The involvement of high glucose concentration in ROS and tyrosine kinase activation hyperglycaemia is further supported by findings that genistein, an antioxidant and non-selective inhibitor of tyrosine kinases, prevented glucosemediated atherogenic modification of low density lipoprotein [120].…”

Comparative Trial of N-Acetyl-Cysteine, Taurine, and Oxerutin on Skin and Kidney Damage in Long-Term Experimental Diabetes

“…Although we are unaware of any studies on the effects of OXE on diabetic complications, inhibition of cataractogenesis has been observed in vitro (41); however, several published reports support beneficial effects of flavonoids against diabetic complications (42,43).…”

A sensitive microextraction by packed sorbent-based methodology combined with ultra-high pressure liquid chromatography as a powerful technique for analysis of biologically active flavonols in wines

“…The flavonoids also act as potent metal chelators and free radical scavengers and are powerful chain-breaking antioxidants [12], and control protein oxidation and advanced glycation end products (AGEs) formation [13]. By acting as free radical scavengers, flavonoids inhibit lipid peroxidation that can initiate LDL oxidation, a contributing factor to the development of atherosclerosis [14][15][16][17][18][19].…”