AIM: To investigate the effect of resveratrol on biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats. METHODS: Resveratrol (RSV) or saline were administered to rats by daily oral gavage for 28 d after sham operation or reversible bile duct obstruction (BDO). Bile was collected 24 h after the last gavage during an intravenous bolus dose of the Mdr1/Mrp2 substrate azithromycin. Bile acids, glutathione and azithromycin were measured in bile to quantify their level of biliary secretion. Liver expression of enzymes and transporters relevant for bile production and biliary secretion of major bile constituents and drugs were analyzed at the mRNA and protein levels using qRT-PCR and Western blot analysis, respectively. The TR-FRET PXR Competitive Binding Assay kit was used to determine the agonism of RSV at the pregnane X receptor. RESULTS: RSV increased bile flow in sham-operated rats due to increased biliary secretion of bile acids (BA) and glutathione. This effect was accompanied by the induction of the hepatic rate-limiting transporters for bile acids and glutathione, Bsep and Mrp2, respectively. RSV also induced Cyp7a1, an enzyme that is crucial for bile acid synthesis; Mrp4, a transporter important for BA secretion from hepatocytes to blood; and Mdr1, the major apical transporter for xenobiotics. The findings were supported by increased biliary secretion of azithromycin. The TR-FRET PXR competitive binding assay confirmed RSV as a weak agonist of the human nuclear receptor PXR, which is a transcriptional regulator of Mdr1/Mrp2. RSV demonstrated significant hepatoprotective properties against BDO-induced cirrhosis. RSV also reduced bile flow in BDO rats without any corresponding change in the levels of the transporters and enzymes involved in RSV-mediated hepatoprotection. CONCLUSION: Resveratrol administration for 28 d has a distinct effect on bile flow and biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats.

• MeSH
• ABC transportéry metabolismus   MeSH
• antiflogistika nesteroidní farmakologie   terapeutické užití   MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• aplikace orální MeSH
• azithromycin farmakokinetika   MeSH
• cholestáza farmakoterapie   etiologie   patofyziologie   MeSH
• glutathion sekrece   MeSH
• hepatocyty účinky léků   metabolismus   sekrece   MeSH
• játra účinky léků   metabolismus   patofyziologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• steroidní receptory agonisté   MeSH
• stilbeny farmakologie   terapeutické užití   MeSH
• žlučové kyseliny a soli chemie   sekrece   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• autistická porucha * etiologie   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• glutathion metabolismus   sekrece   MeSH
• lidé MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• methionin antagonisté a inhibitory   MeSH
• rtuť analýza   metabolismus   škodlivé účinky   MeSH
• těhotenství účinky léků   MeSH
• thimerosal škodlivé účinky   toxicita   MeSH
• vakcinace škodlivé účinky   MeSH
• zubní amalgam škodlivé účinky   toxicita   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• těhotenství účinky léků   MeSH
• ženské pohlaví MeSH

• MeSH
• glutathion metabolismus   sekrece   MeSH
• kolchicin škodlivé účinky   MeSH
• morčata MeSH
• otrava MeSH
• Check Tag
• morčata MeSH

• Konspekt
• Experimentální medicína
• NLK Obory
• toxikologie
• experimentální medicína
• NLK Publikační typ
• studie