Resveratrol glucuronides

The metabolites of [3H] /ra ,v-resveratrol detected in tissues and plasma were also investigated. In kidney, liver, heart, lungs, brain, and plasma (2-h samples), the only metabolite found was resveratrol glucuronide. Glucuronides in plasma and kidney disappeared completely at 18 h. In lungs, liver, heart, and brain, the main detected metabolite at 18 h was the /ra ,v-resveratrol (Table 13.2). This study provided data on the metabolic fate of resveratrol. While glucuronides were predominant in plasma and tissues at the earlier times, the aglycone represented the main form at later times [El-Mohsen et al., 2006]. 

Similarly in 2005, Wang et al. identified the microbial metabolites of resvera-trol in rats (Table 13.3). Urine samples were obtained after oral administration of 20 mg/kg to Sprague-Dawley rats. They identified resveratrol-glucuronide, resveratrol-sulfate, 7,8-dihydroresveratrol, and 7,8-dihydroresveratrol-sulfate as the main 12-h urinary metabolite in rats by mass spectrometry after are SPE treatment [Wang et al., 2005]. 

There is a further pharmacokinetic study in which /ruH.v-resveratrol in the aglycone form and the glucuronide forms were examined following intravenous (15 mg/kg) and oral (50 mg/kg) administration of /rau.v-resveratrol to rats [Marier et al., 2002], After intravenous administration, the plasmatic resveratrol concentrations declined rapidly over the first 2 h. Then, concentration profiles of resveratrol and resveratrol glucuronide from intravenous or oral administration increased abruptly due to enterohepatic recirculation over the 4- to 8-h time period that resulted in a significant maintenance in the terminal elimination... 

Urinary excretion mainly took place in the first 4 h after consumption (77% of total excretion), although resveratrol metabolites remained in urine between 12and24 h after intake. Free resveratrol, 2 glucuronides, and the 3-sulfate excreted in the urine 24 h after intake were below 0.04, 2, 9, and 11 % of the 0.5 mg provided, respectively. At higher dose (5 mg) resveratrol, glucuronides and sulfate recoveries in the urine at 24 h were 0.1, 0.5, 3, and 5% of the dose, respectively. In urinary excretion, the sulfate forms were also higher than the glucuronide and free forms. 

Kuhnle G, Spencer JPE, Chowrimootoo G, Schroeter H, Debnam ES, Srai SKS, Rice-Evans C, Hahn U. 2000. Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 272 212-217. 

Zamora-Ros et al [2006] carried out the first work that assessed the bioavailability of resveratrol (provided by different wines) in a regular intervention during 28 day. The analyses were performed by LC-MS/MS. In the first study, 10 healthy males were recruited to consume 300 mL/day of sparkling wine (1.19 mg resveratrol/1). After 28 day of supplementation, urinary trans-and m-resveratrol-3-O-glucuronides were 75 and 38 nmol/g creatinine, respectively. In the second study, 10 healthy females were selected to consume 200 mL of white wine (1.99 mg resveratrol/L) or 200 mL of red wine (12.8 mg resveratrol/L) in a crossover clinical trial. Likewise after 28 days only resveratrol metabolites were detected in morning urine, trans- (205 and 473 nmol/g creatinine) and ra-resveratrol-3-O-glucuronidcs (58 and 140 nmol/g creatinine) were found after white and red wine intake, respectively. Those studies showed that urinary excretion was dose dependent. Furthermore, slight amounts of resveratrol metabolites were also detected at baseline periods. No free resveratrol or piceid were detected in any of the studies. 

Aumont V, Krisa S, Battaglia E, Netter P, Richard T, Merillon JM, Magdalou J, Sabolovic N. 2001. Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human. Arch Biochem Biophys 393 281-289. 

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