High soy diets reduce injury in rat models of focal cerebral ischemia and are proposed as alternatives to hormone replacement therapy for postmenopausal women. The present study tests the hypothesis that the major soy isoflavone genistein and the daidzein metabolite equol are neuroprotective in transient focal cerebral ischemia in male and ovariectomized female rats by inhibiting oxidative stress. Genistein is the primary circulating soy isoflavones in humans, whereas equol is the primary circulating isoflavone in rats. Male and ovariectomized (OVX) female Sprague-Dawley rats were fed an isoflavone reduced diet alone or supplemented with genistein (500 ppm) or equol (250 ppm) for two weeks prior to 90 minutes transient middle cerebral artery occlusion followed by reperfusion under isofluorane anesthesia. Indices of oxidative stress were determined 24 hours after reperfusion, and cerebral injury was evaluated three days after reperfusion. Genistein and equol significantly reduced infarct size in both sexes. Further studies in OVX female rats revealed that this neuroprotection was accompanied by a decrease in NAD(P)H oxidase activity and superoxide levels in the brain. In addition, equol reduced plasma thiobarbituric acid reactive substances. There were no significant differences in cerebral blood flow among treatment groups. In conclusion, dietary soy isoflavones are neuroprotective in transient focal cerebral ischemia in male and OVX female rats. These isoflavones may protect the brain via increases in endogenous antioxidant mechanisms and reduced oxidative stress.
- brain ischemia
- oxidative stress
- NADPH oxidase
- Copyright © 2010, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology