Resveratrol modifies biliary secretion of cholephilic compounds in sham-operated and cholestatic rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10364876" target="_blank" >RIV/00216208:11160/17:10364876 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11150/17:10364876

Výsledek na webu

<a href="http://www.wjgnet.com/1007-9327/full/v23/i43/7678.htm" target="_blank" >http://www.wjgnet.com/1007-9327/full/v23/i43/7678.htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3748/wjg.v23.i43.7678" target="_blank" >10.3748/wjg.v23.i43.7678</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Resveratrol modifies biliary secretion of cholephilic compounds in sham-operated and cholestatic rats

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Resveratrol modifies biliary secretion of cholephilic compounds in sham-operated and cholestatic rats

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centrum interakcí potravních doplňků s léčivy a nutrigenetiky</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

World Journal of Gastroenterology

ISSN

1007-9327

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

43

Stát vydavatele periodika

CN - Čínská lidová republika

Počet stran výsledku

15

Strana od-do

7678-7692

Kód UT WoS článku

000415703800004

EID výsledku v databázi Scopus

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