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SECOND INTERNATIONAL SYMPOSIUM
ON THE ROLE OF SOY
IN PREVENTING AND TREATING CHRONIC DISEASE

September 15-18, 1996
Brussells, Belgium

SCIENTIFIC PROGRAM
(Oral Abstracts)

Soy and Heart Disease : Effects Independent of Cholesterol Reduction

Genistein Inhibits Reactive Oxygen Species (ROS) Formation During Activation of Rat Platelets in Whole Blood
N.W. Schoene and C.A. Guidry. Nutrient Requirements & Functions Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, MD 20705.

Isoflavones in soy may lower the morbidity and mortality of cardiovascular disease by decreasing thrombotic processes in platelets. A complex series of sequential reactions occur as platelets are activated with the production of second messengers that act as amplifiers of original signals. Increases in activities of cytosolic tyrosine kinases occur very rapidly during initial stages of platelet activation. Reactive oxygen species (ROS), produced during collagen stimulation of platelets, can amplify signals mediated by the cytosolic protein tyrosine kinases, possibly by inhibiting phosphatase(s) and permitting activating protein tyrosine phosphate residues to accumulate. Increases in phosphorylated tyrosine residues would result in an increased production of additional amplifiers, thereby promoting platelet aggregation. We added genistein, an isoflavone and purported tyrosine kinase inhibitor, to whole blood samples from rats and followed the collagen-induced production of ROS in platelets with flow cytometry. This method utilizes the probe 2',7'-dichlorofluorescin diacetate to detect receptor-mediated production of ROS in platelets in whole blood. Pretreatment of diluted blood samples with genistein resulted in a dose-dependent inhibition of the collagen-induced increase in ROS (expressed as % inhibition/ M genistein; 40%*/10 M; 65%/35 M; 65%/70 M; respectively, n 10, *p=0.001). In agreement with these results, genistein (140 M in undiluted samples) produced at 51% decrease in collagen-simulated shape change and reduced aggregation by 57% (74% aggregation, collagen alone; 27% aggregation, genistein plus collagen; n=8, p=0.005). However, pleiotropic antioxidant effects to either reduce ROS and/or protect tyrosine phosphatase(s) could also contribute to decreases in phosphorylation signals. Further experiments are required to detemine which mechanism(s) produces the decrease in platelet aggregatory responses. This potential for antithrombotic action makes it important to obtain more information on how dietary isoflavones contribute to a prolongation of health and a diminution in the development of chronic diseases.

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