Effects of some natural 5-hydroxy-isoflavones on cultured human endothelial cells in presence and absence of hydrogen peroxide.
Due to their biological activity, it has been suggested that consumption of isoflavone-rich diets may prevent prostate and breast cancers, osteoporosis and cardiovascular diseases. Preventive effects of isoflavones on cancer and cardiovascular diseases have been associated with their oestrogenic and antioxidant properties. However, concerns still exist about the potential dangers of consuming high levels of these compounds, since it is known that some of them have cytostatic or cytotoxic properties, depending on the concentration. To evaluate the potential cytotoxic risk and antioxidant benefit of natural 5-hydroxy-isoflavones (5-OH-isoflavones) for human vascular endothelium, the effect of some natural 5-OH-isoflavones was evaluated on cultured human endothelial cells, in the presence and absence of H(2)O(2) (3 mM for 4 h). None of the isoflavones tested were able to prevent oxidative damage to endothelial cells at maximal extracellular concentrations of 1 mM. The low antioxidant capacity of these compounds was also shown by the DPPH (1,1-diphenyl-2-picrylhydrazyl radical) method. On the other hand, genistein and biochanin A, having a free 7-OH group, were toxic to the human endothelial cells in a dose-dependent manner, at concentrations >or=300 microM and >or= 100 microM, respectively. These results indicate that the non-specific cytotoxic effect of 5-OH-isoflavones is associated with the free 7-OH group. In conclusion, we were not able to show that 5-OH-isoflavones are beneficial to human endothelial cells when the cells were exposed to oxidative stress caused by 3 mM of H(2)O(2), but it can be concluded that consumption of 5-OH-isoflavones is of no direct cytotoxic risk to the human vascular endothelium since toxic concentrations are believed to be unreachable in-vivo.
Paulo
Alexandra
A
CECF, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649 003 Lisboa, Portugal. mapaulo@ff.ul.pt
Mota-Filipe
Helder
H
D000975:Antioxidants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress; D010851:Picrates
D000975:Antioxidants; D001713:Biphenyl Compounds; D006834:Hydrazines; D007529:Isoflavones; D010851:Picrates; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl