Dietary genistein and equol (4′, 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia

Ma Yulin, Jennifer C. Sullivan, Derek Schreihofer

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44 Citations (Scopus)

Abstract

High soy diets reduce injury in rat models of focal cerebral ischemia and are proposed as alternatives to hormone replacement therapy for post-menopausal 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 (OVX) female rats by inhibiting oxidative stress. Genistein is the primary circulating soy isoflavone in humans, whereas equol is the primary circulating isoflavone in rats. Male and OVX female Sprague-Dawley rats were fed an isoflavone-reduced diet alone or supplemented with genistein (500 ppm) or equol (250 ppm) for 2 wk prior to 90-min transient middle cerebral artery occlusion followed by reperfusion under isoflurane anesthesia. Indices of oxidative stress were determined 24 h after reperfusion, and cerebral injury was evaluated 3 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, and neurological deficits up to 7 days after injury. 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number3
DOIs
StatePublished - 1 Sep 2010

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Equol
Isoflavones
Genistein
Brain Ischemia
Oxidative Stress
Transient Ischemic Attack
Reperfusion
Cerebrovascular Circulation
Diet
Estrogen Replacement Therapy
Thiobarbituric Acid Reactive Substances
NADPH Oxidase
Isoflurane
Middle Cerebral Artery Infarction
Wounds and Injuries
Brain
Reperfusion Injury
Superoxides
Sprague Dawley Rats
Anesthesia

Keywords

  • Brain ischemia
  • NADPH oxidase
  • Phytoestrogen

Cite this

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title = "Dietary genistein and equol (4′, 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia",
abstract = "High soy diets reduce injury in rat models of focal cerebral ischemia and are proposed as alternatives to hormone replacement therapy for post-menopausal 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 (OVX) female rats by inhibiting oxidative stress. Genistein is the primary circulating soy isoflavone in humans, whereas equol is the primary circulating isoflavone in rats. Male and OVX female Sprague-Dawley rats were fed an isoflavone-reduced diet alone or supplemented with genistein (500 ppm) or equol (250 ppm) for 2 wk prior to 90-min transient middle cerebral artery occlusion followed by reperfusion under isoflurane anesthesia. Indices of oxidative stress were determined 24 h after reperfusion, and cerebral injury was evaluated 3 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, and neurological deficits up to 7 days after injury. 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.",
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N2 - High soy diets reduce injury in rat models of focal cerebral ischemia and are proposed as alternatives to hormone replacement therapy for post-menopausal 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 (OVX) female rats by inhibiting oxidative stress. Genistein is the primary circulating soy isoflavone in humans, whereas equol is the primary circulating isoflavone in rats. Male and OVX female Sprague-Dawley rats were fed an isoflavone-reduced diet alone or supplemented with genistein (500 ppm) or equol (250 ppm) for 2 wk prior to 90-min transient middle cerebral artery occlusion followed by reperfusion under isoflurane anesthesia. Indices of oxidative stress were determined 24 h after reperfusion, and cerebral injury was evaluated 3 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, and neurological deficits up to 7 days after injury. 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.

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