title: Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with α-tocopherol.
abstract: Vitamin E and polyphenols could exhibit a therapeutic role in the treatment of oxidative stress-induced neurodegenerative diseases. Therefore, their ability to cross the blood-brain barrier (BBB) represents an important issue to be explored by different diet combinations. In this study, we have evaluated the ability of α-tocopherol to support epigallocatechin-3-gallate (EGCG), quercetin and rutin to cross the BBB, following oral administration. Eighteen rats were fed a standard diet (C), a diet supplemented with α-tocopherol (A), with a mixture of EGCG, quercetin and rutin (P); or with a mixture of α-tocopherol and the three flavonoids (AP). Flavonoids and their conjugated derivatives were assayed in brain and plasma by HPLC-MS, whereas α-tocopherol was detected by RP-HPLC. The oxidative damage, due to the potential pro-oxidant activity of flavonoids, was evaluated by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hippocampal Cornus Ammonis, one of the most vulnerable sites in the brain. Our results indicate that α-tocopherol is able to promote quercetin transport across the BBB. The mixture of rutin and quercetin seems to favour the accumulation of quercetin and/or its conjugated derivatives in the brain. In contrast, α-tocopherol does not affect EGCG transport across the BBB. The densitometric analysis of 8-OHdG immunoreactivity does not reveal any difference of oxidative damage among the experimental groups. Our results suggest that α-tocopherol may promote quercetin transport across the BBB, leading to a significant increase of α-tocopherol and quercetin concentration in the brain.
authors.affiliation: Department of Earth, Life and Environmental Sciences, University of Urbino "Carlo Bo", Via Ca' Le Suore 2/4, 61029 Urbino, PU, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ferri
authors.forename: Donato
authors.initials: D
authors.lastname: Angelino
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gennari
authors.forename: Serena
authors.initials: S
authors.lastname: Benedetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ambrogini
authors.forename: Paolo
authors.initials: P
authors.lastname: Del Grande
authors.forename: Paolino
authors.initials: P
authors.lastname: Ninfali
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000502:physiology*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D006624:Hippocampus / Q000502:physiology; D008297:Male; D013058:Mass Spectrometry; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D012431:Rutin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D003849:Deoxyguanosine; D024502:alpha-Tocopherol