Marie-Claude Menet1,2, Stephanie Baron3,4, Meryam Taghi1, Remi Diestra3, Delphine Dargère5, Olivier Laprévote5, Valérie Nivet-Antoine6,7, Jean-Louis Beaudeux7,8, Tatiana Bédarida3, Charles-Henry Cottart3,7,9. 1. INSERM, UMR-S 1144, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France. 2. AP-HP, G.H. Cochin, Broca, Hôtel-Dieu, Paris, France. 3. Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France. 4. AP-HP, Hôpital Européen Georges Pompidou, Paris, France. 5. CNRS, UMR 8638, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France. 6. UMR-S1140, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France. 7. AP-HP, G.H. Necker - Enfants malades, Paris, France. 8. UMR-S 1139, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, France. 9. INSERM U 1151, Institut Necker-Enfants Malades - INEM, Paris, France.
Abstract
SCOPE: 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. METHODS AND RESULTS: 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.
SCOPE: 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. METHODS AND RESULTS: 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.
Authors: Michaela Böhmdorfer; Akos Szakmary; Robert H Schiestl; Javier Vaquero; Juliane Riha; Stefan Brenner; Theresia Thalhammer; Thomas Szekeres; Walter Jäger Journal: Nutrients Date: 2017-12-12 Impact factor: 5.717