Endocrine Abstracts (2004) 7 P57

Protective effects of phytoestrogens against oxidative stress in human endothelial cells

W Zhong, IP Adams, RL Adams & SL Atkin

Division of Academic Medicine, University of Hull Postgraduate Medical Institute, Hull, UK.

Background Phytoestrogens are a group of biologically active plant substances with chemical structures similar to that of endogenous estrogen. Their beneficial effects on cardiovascular protection have been indicated by the relatively lower incidence of cardiovascular diseases in people with higher phytoestrogen consumption. Recent studies show that they have anti-oxidative properties, which have not been studied in human endothelial cells under different glucose conditions.

Methods Human umbilical vein endothelial cells were subjected to hydrogen peroxide induced oxidative stress with and without the presence of 100 nM genistein or daidzein under normal (5 mM) and high glucose conditions (25 mM). The effects on apoptosis and cellular proliferation were subsequently determined using a cell death ELISA, tritiated thymidine incorporation and WST assays. The pure anti-estrogen ICI-182780 was subsequently used to block activation of estrogen receptors by phytoestrogens.

Results Genistein and daidzein significantly reduced hydrogen peroxide-induced apoptotic DNA fragmentation by 56.3 percent and 42.6 percent respectively, and genistein reversed hydrogen peroxide-induced inhibition of proliferation by 40.3 percent under normal glucose condition. The protection provided by genistein was significantly reduced, and that of daidzein lost, in high glucose conditions. Finally, the protective effects of these phytoestrogens were completely blocked by 50nM of the pure anti-estrogen ICI-182780.

Conclusion Phytoestrogens protected endothelial cells against oxidative stress-

induced apoptotic DNA damage and cell proliferation inhibition under both normal and high glucose conditions. This protection was significantly reduced by high glucose. An anti-estrogen blocked the protective effects of phytoestrogens, indicating that they exert the anti-oxidative properties through interaction with estrogen receptors. These data give further in vitro evidence that phytoestrogens may confer clinical cardiovascular protection through activation of the estrogen receptor that this effect may be abrogated by hyperglycaemia.

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