Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver

Mol Nutr Food Res. 2017 Aug;61(8). doi: 10.1002/mnfr.201600686. Epub 2017 Mar 21.

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.

Keywords: Administration; Distribution; Metabolites; Mice; Resveratrol.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Chromatography, High Pressure Liquid / methods
  • Glucuronides / pharmacokinetics*
  • Heart / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Mass Spectrometry / methods
  • Mice
  • Resveratrol
  • Stilbenes / metabolism
  • Stilbenes / pharmacokinetics*
  • Tissue Distribution

Substances

  • Glucuronides
  • Stilbenes
  • dihydroresveratrol
  • resveratrol-4'-O-glucuronide
  • Resveratrol