Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver.
Trans-resveratrol is widely studied for its potentially beneficial effects on numerous disorders. It is rapidly metabolized and its metabolites can exhibit biological activity. The present study aimed to investigate whether acute or sustained trans-resveratrol administration impacted on the distribution of trans-resveratrol and its metabolites in brain, heart, and liver.



We used ultra-HPLC quadrupole-TOF (UHPLC-Q-TOF) in a full-scan mode to identify and assess large numbers of resveratrol metabolites. For acute intake, mice were overfed with a single dose of trans-resveratrol (150 mg/kg) and organs were collected after 30 and 60 min. For sustained intake, trans-resveratrol was given in the chow (0.04% w/w corresponding to 40 mg/kg/day), and plasma and the organs were collected after 3 months of this resveratrol diet. We found that trans-resveratrol-3-O-glucuronide and resveratrol-3-sulfate were the main metabolites found after acute intake, and free trans-resveratrol (in the brain and heart) and dihydroresveratrol derivatives were found after sustained administration CONCLUSIONS: Our results show notable differences between acute and sustained administration of trans-resveratrol and distribution of trans-resveratrol and its metabolites in mouse heart, brain, and liver. The results suggest a strategy for development of galenic forms of resveratrol.
INSERM, UMR-S 1144, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.|AP-HP, G.H. Cochin, Broca, Hôtel-Dieu, Paris, France.
Marie-Claude
MC
Menet
Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.|AP-HP, Hôpital Européen Georges Pompidou, Paris, France.
Stephanie
S
Baron
INSERM, UMR-S 1144, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.
Meryam
M
Taghi
Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.
Remi
R
Diestra
CNRS, UMR 8638, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France.
Delphine
D
Dargère
CNRS, UMR 8638, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France.
Olivier
O
Laprévote
UMR-S1140, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France.|AP-HP, G.H. Necker - Enfants malades, Paris, France.
Valérie
V
Nivet-Antoine
AP-HP, G.H. Necker - Enfants malades, Paris, France.|UMR-S 1139, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France.
Jean-Louis
JL
Beaudeux
Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.
Tatiana
T
Bédarida
Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.|AP-HP, G.H. Necker - Enfants malades, Paris, France.|INSERM U 1151, Institut Necker-Enfants Malades - INEM, Paris, France.
Charles-Henry
CH
Cottart
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D020719:Glucuronides / Q000493:pharmacokinetics*; D006321:Heart / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D020719:Glucuronides; D013267:Stilbenes; C544754:dihydroresveratrol; C499731:resveratrol-4'-O-glucuronide; D000077185:Resveratrol
Administration; Distribution; Metabolites; Mice; Resveratrol