cis- and trans-Resveratrol are glucuronidated in rat brain, olfactory mucosa and cultured astrocytes.
OBJECTIVE
Glucuronidation of cis- and trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is a naturally occurring phytoalexin known to exert a number of beneficial health effects, was investigated in rat brain, cultured astrocytes and olfactory mucosa.


METHODS
The isomers were incubated with tissue homogenates, microsomes, or rat liver recombinant UDP-glucuronosyltransferases in the presence of UDP-glucuronic acid. The glucuronides were separated by HPLC and quantitated. Astrocytes were exposed to lipopolysaccharide to promote inflammatory conditions.


RESULTS
All tissues were able to form resveratrol glucuronides although at a lower extent, when compared to the liver. The reaction was stereo- and regioselective. In brain tissue, trans-resveratrol 3-O-glucuronide was mainly formed, whereas the cis-isomer was glucuronidated at a lower rate on that position. No 4'-O-glucuronide was detected in brain. In olfactory mucosa homogenates, the cis 3-O-glucuronide was mainly formed, whereas the trans-isomer was glucuronidated only on the 3-position. In astrocytes, 3-O-glucuronides of the cis- and trans-resveratrol were only detected. The rat recombinant UGT1A6 and UGT2B1 isoforms were able to glucuronidate cis- and trans-resveratrol. Finally, in inflammatory conditions, trans-resveratrol glucuronidation was enhanced in astrocytes.


CONCLUSIONS
Brain tissues are effective in the glucuronidation of resveratrol isomers. This metabolism pathway is likely to modulate the concentration of these biologically active substances.
Sabolovic
Nicole
N
UMR 7561 CNRS-Université Henri Poincaré Nancy 1, Faculté de Médecine, Vandoeuvre-lès-Nancy, et Université Victor Segalen, Bordeaux, France. nicole.sabolovic@medecine.uhp-nancy.fr
Heurtaux
Tony
T
Humbert
Anne-Claude
AC
Krisa
Stéphanie
S
Magdalou
Jacques
J
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D020719:Glucuronides / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism*
D020719:Glucuronides; D007527:Isoenzymes; D011994:Recombinant Proteins; D013267:Stilbenes; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7; D000077185:Resveratrol