Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil.
Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.
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Laboratory of Neurosciences, National Institutes on Aging, National Institutes of Health, Bethesda, MD 20892-1582, USA.
Drieu
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Grange
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Chang
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Rapoport
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Purdon
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D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism*; D005419:Flavonoids; D005849:Gerbillinae; D020441:Ginkgo biloba / Q000737:chemistry*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019308:Palmitic Acid / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010936:Plant Extracts; D010946:Plants, Medicinal; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D014851:Wakefulness; D000096983:Ginkgo Extract
D016718:Arachidonic Acid; D005227:Fatty Acids; D005419:Flavonoids; D008563:Membrane Lipids; D018696:Neuroprotective Agents; D019308:Palmitic Acid; D010743:Phospholipids; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract