Tissular Distribution and Metabolism of trans-ε-Viniferin after Intraperitoneal Injection in Rat

Background: Recent studies showed that trans-ε-viniferin (ε-viniferin), a trans-resveratrol dehydrodimer, has anti-inflammatory and anti-obesity effects in rodents. The main purpose of this work was to assess the tissue distribution study of ε-viniferin and its metabolites after intraperitoneal (IP) administration in rat. Methods: After IP injection of 50 mg/kg, ε-viniferin and its metabolites were identified and quantified in plasma, liver, kidneys, adipose tissues, urine, and faeces by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). Results: ε-Viniferin underwent a rapid hepatic metabolism mostly to glucuronides but also to a lesser extent to sulphate derivatives. The highest glucuronide concentrations were found in liver followed by plasma and kidneys whereas only traces amounts were found in adipose tissues. In contrast the highest ε-viniferin areas under concentration (AUC) and mean residence times (MRT) values were found in white adipose tissues. Finally, much lower levels of ε-viniferin or its metabolites were found in urine than in faeces, suggesting that biliary excretion is the main elimination pathway. Conclusion: A rapid and large metabolism of ε-viniferin and a high bioaccumulation in white adipose tissues were observed. Thus, these tissues could be a reservoir of the native form of ε-viniferin that could allow its slow release and a sustained presence within the organism.