+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Different protective effects of tauroursodeoxycholate, ursodeoxycholate, and 23-methyl-ursodeoxycholate against taurolithocholate-induced cholestasis



Different protective effects of tauroursodeoxycholate, ursodeoxycholate, and 23-methyl-ursodeoxycholate against taurolithocholate-induced cholestasis



Digestive Diseases & Sciences. 41(2): 250-255



The coinfusion of tauroursodeoxycholate (TUDC) prevents taurolithocholate (TLC)-induced cholestasis. 23-Methyl-ursodeoxycholate (MUDC) is a side-chain derivative of ursode-oxycholate (UDC). If conjugation with taurine is important for the protective effect of UDC, then MUDC may not be as able as TUDC to prevent TLC-induced cholestasis since it is poorly amidated by the liver. To answer this question, isolated livers of adult Sprague-Dawley rats were coinfused with MUDC (UDC, TUDC) and TLC. After 15 min, inflow rates of the bile acids were doubled. In further experiments taurine in excess was added to the coinfused bile acids. The uptake of bile acids was gt 90% in all groups, irrespective of whether they were perfused alone or in combination. Single perfusion of TLC caused a rapid decrease in bile flow. UDC and MUDC were hypercholeretic: TUDC moderately choleretic. During coinfusion experiments, TUDC not only completely abolished chotestasis but in addition increased bile flow and biliary bile acid secretion. UDC did prevent TLC cholestasis at the lower inflow rates. At high inflow rates, bile flow decreased significantly. Addition of taurine to this bile acid combination did not significantly improve the anticholestatic effect of UDC. At low and high infusion rates of MUDC, cholestasis induced by TLC was reduced very little. Cumulative bile flow over 30 min fell by apprxeq 70% as compared to that of singly perfused MUDC. Addition of taurine to the coinfused MUDC/TLC slightly, but significantly, improved the anticholestatic effect of MUDC. Since MUDC is by far less protective than UDC (and TUDC) despite similar physicochemical properties, it is concluded that taurine conjugation of UDC seems to be a prerequisite to prevent TLC-induced cholestasis. The results imply that treatment of cholestatic liver diseases with taurine-conjugated UDC might be more appropriate than with unconjugated UDC in cases where taurine conjugation is defective or where taurine depletion has occurred.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 008468471

Download citation: RISBibTeXText

PMID: 8601366

DOI: 10.1007/bf02093812


Related references

23 methylursodeoxycholate is much less protective than ursodeoxycholate against taurolithocholate induced cholestasis. Gastroenterology 100(5 PART 2): 719, 1991

Taurine conjugation is necessary for the protective effect of ursodeoxycholate in taurolithocholate induced cholestasis. Journal of Hepatology 9(SUPPL 1): S82, 1989

Tauroursodeoxycholate increases rat liver ursodeoxycholate levels and limits lithocholate formation better than ursodeoxycholate. Gastroenterology 109(2): 564-572, 1995

In vivo administration of an intracellular ca2+ chelator and a pkc inhibitor to bile duct ligated , vagotomized rats abolishes the protective effects of ursodeoxycholate and tauroursodeoxycholate against vagotomy induced duct damage. Digestive Disease Week Abstracts & Itinerary Planner : Abstract No S929, 2003

Inhibition of Na+/H+ exchange in the rat is associated with decreased ursodeoxycholate hypercholeresis, decreased secretion of unconjugated ursodeoxycholate, and increased ursodeoxycholate glucuronidation. Gastroenterology 95(2): 454-463, 1988

Ursodeoxycholate inhibits the mitochondrial membrane permeability transition induced by glycochenodeoxycholate A mechanism for ursodeoxycholate cytoprotection?. Hepatology 20(4 PART 2): 175A, 1994

Lithocholate-3-O-glucuronide-induced cholestasis. A study with congenital hyperbilirubinemic rats and effects of ursodeoxycholate conjugates. Digestive Diseases and Sciences 38(8): 1543-1548, 1993

Tauroursodeoxycholate prevents taurolithocholate-induced cholestasis and toxicity in rat liver. Journal of Hepatology 10(3): 280-283, 1990

Effects of ursodeoxycholate udc taurine t and ursodeoxycholate plus taurine udc plus t on serum enzyme levels in patients with chronic hepatitis. Hepatology 7(5): 1110, 1987

Uptake of ursodeoxycholate and tauroursodeoxycholate in isolated rat hepatocytes. Hepatology 5(5): 983, 1985

The ursodeoxycholate dose-dependent formation of ursodeoxycholate-glucuronide in the rat and the choleretic potencies. Hepatology 11(5): 743-749, 1990

Hepatoprotection with tauroursodeoxycholate and muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways. Gut 51(1): 113-119, 2002

Ursodeoxycholate as well as tauroursodeoxycholate enhances the biliary transport maximum of sulfobromophthalein in the rat. Hepatology 5(5): 975, 1985

Protection against taurolithocholate-induced cholestasis by muricholate, tauroursodeoxycholate, or DBcAMP Involvement of intracellular signaling mechanisms. Hepatology 32(4 Pt 2): 429A, 2000

Hepatoprotection with tauroursodeoxycholate and beta muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways. Gut 51(1): 113-119, 2002