Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.
1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability.
Department of Neurosciences, Medical School, Pisa, Italy.
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De Santi
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Pietrabissa
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Spisni
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Mosca
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Pacifici
D000328:Adult; D000368:Aged; D001682:Biological Availability; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008528:Mefenamic Acid / Q000494:pharmacology; D008875:Middle Aged; D015394:Molecular Structure; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D000077185:Resveratrol; D019685:Rosales / Q000737:chemistry*; D020156:Salicylic Acid / Q000494:pharmacology; D013267:Stilbenes / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014920:Wine
D013267:Stilbenes; D013431:Sulfates; D008528:Mefenamic Acid; D010724:Phosphoadenosine Phosphosulfate; D011794:Quercetin; D015238:Sulfotransferases; D020156:Salicylic Acid; D000077185:Resveratrol