Estradiol-17β-D-glucuronide (E-17G) cholestasis in perfused rat liver: Fate of E-17G and choleretic responses to bile salts

✍ Scribed by Riccardo Utili; Marie F. Tripodi; Luigi E. Adinolfi; Giovanni B. Gaeta; Dr. Charles O. Abernathy; Hyman J. Zimmerman

• Book ID: 102848581
• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 964 KB
• Volume: 11
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840110505

✦ Synopsis

This study was designed to test the hypothesis that increasing the infusion rate of bile salts could overcome drug-induced cholestasis. Cholestasis was induced by administration of 17.5 pmol/L estradiol-17;le-~-glucuronide during the infusion of taurocholate, tauroursodeoxycholate or dehydrocholate at 20 nmol/min/gm liver. After 30 min, a bolus of 10 pmol of the bile salts was added to the perfusate, and the infusion rate of each bile salt was increased. Taurocholate at a rate of 62 or 125 nmol/min/gm liver, caused a prompt dose-dependent increase of the depressed bile flow and bile salt excretion. A higher rate of taurocholate infusion (180 nmol/min/gm liver) was less effective than either the 62 or 125 rate in increasing bile flow. Infusion of tauroursodeoxycholate at 250 or 390 nmol/min/gm liver also led to a dose-dependent recovery. Further increase of tauroursodeoxycholate infusion rate to 580 nmol/min/gm liver did not provide any additional recovery in bile flow. Dehydrocholate, at rates of 62 or 125 nmol/min/gm liver, gave only a slight enhancement of bile flow. Both taurocholate and tauroursodeoxycholate caused a marked removal of the estradio~-l7;le-~-g~ucuronide, which had accumulated in the liver. At lower taurocholate infusion rates, the estradio~-l7;le-~-g~ucuro~de was excreted mainly in the bile. At the highest rate, however, biliary excretion of estradiol-17;le-~-glucuronide declined signifi- cantly, and a marked back-efflux of the estrogen into the perfusate was noted. In contrast, taurourmdeoxycholate led to enhanced biliary estradiol-17;le-n-