Some aspects of thein vivo neuroprotective capacity of flavonoids: Bioavailability and structure-activity relationship
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On the basis of previous work showing that flavonoids structurally related to quercetin are neuroprotective for cells in culture, this work was directed towards determining if several flavonoids (quercetin, fisetin and catechin) could acutely and by an intraperitoneal (IP) route reach significant cerebral concentrations and either prevent or facilitate recovery from a brain lesion induced by focal ischemia in rats.
Aqueous and liposomal preparations of quercetin, fisetin and catechin were administered IP in a single dose and assessed in the brain by HPLC at 30 min, 1 h, 2 h and 4 h. Ischemic damage from focal middle cerebral artery occlusion was assessed spectrophotometrically with 2,3,5,-triphenylltetrazolium chloride (TTC). Infarct volume was assessed by an image analysis system following perfusion with TTC. The status of the cerebral tissue was evaluated by hematoxylin-eosin.
Flavonoids administered in aqueous preparations were undetected in the brain. Cerebral concentrations of catechin (10.5 ng/g), fisetin (8.23 ng/g) and quercetin (509 ng/g) were detected in the brain only after IP injection of the liposomal preparations. Spectrophotometric analysis of brain tissue with the TTC-technique showed that liposomal quercetin reduced ischemic damage and infarct volume after permanent occlusion of the middle cerebral artery (ischemic: 41.3 mm3 vs liposomal quercetin: 17 mm3). In liposomal quercetin-treated animals there was also recovery of the cytoarchitecture in ischemic areas of striatum and cortex. Although a liposomal preparation of fisetin had similar effects, catechin failed to protect brain tissue.
In conclusion, early administration of liposomal preparations of quercetin and structurally related flavonoids are beneficial and neuroprotective in experimental focal ischemia.
- Some aspects of thein vivo neuroprotective capacity of flavonoids: Bioavailability and structure-activity relationship
Volume 6, Issue 7-8 , pp 543-553
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- 1. Department of Neurochemistry, Instituto de Investigaciones Biológicas, Avenida Italia, 3318, Clemente Estable, Montevideo, Uruguay
- 2. Department of Pathology, Faculty of Medicine, Universidad de la República, Avenida Italia s/n, Montevideo, Uruguay