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Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat
Author(s) -
Chen TzuYing,
Ferruzzi Mario G.,
Wu QingLi,
Simon James E.,
Talcott Stephen T.,
Wang Jun,
Ho Lap,
Todd George,
Cooper Bruce,
Pasinetti Giulio M.,
Janle Elsa M.
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700111
Subject(s) - bioavailability , pharmacokinetics , chemistry , polyphenol , quercetin , resveratrol , catechin , diabetes mellitus , urine , cmax , pharmacology , excretion , endocrinology , medicine , biochemistry , antioxidant
Scope The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model. Methods and results (ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8‐h pharmacokinetic study was performed. After 24 h, a second dose of SGP was administered and 1 h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished C max for all catechin, epicatechin, quercetin and resveratrol conjugated metabolites. Bioavailability was significantly lower in ZDF rats for methylated flavan‐3‐ol, RES, and quercetin metabolites. Significantly lower levels of metabolites of RES, quercetin, and flavan‐3‐ols were found in brains of ZDF rats. There was no significant difference between ZDF and LN in anthocyanins in plasma and no anthocyanins were detectable in brain extracts. ZDF rats showed significantly higher urinary excretion for all polyphenols. Conclusion Diabetes may alter the overall bioavailability of some polyphenols in plasma and brain in part due to higher urinary clearance.