Literature DB >> 8174892

Ursodeoxycholate conjugates protect against disruption of cholesterol-rich membranes by bile salts.

D M Heuman1, R Bajaj.   

Abstract

BACKGROUND/AIMS: Ursodeoxycholic acid attenuates hepatocellular injury in cholestatic disorders, possibly by counteracting membrane disruptive effects of endogenous bile salts. The possible physicochemical basis of this protective effect was explored by using model membranes composed of egg phosphatidylcholine and cholesterol.
METHODS: Large unilamellar vesicles containing trapped 3H inulin were prepared by extrusion and gel filtration. Vesicle disruption (release of trapped inulin) was quantified using rapid centrifugal ultrafiltration.
RESULTS: Disruption of membranes increased with bile salt concentration, hydrophobicity, and increasing ionic strength. Disruption decreased with a decreasing bile salt/phospholipid ratio or an increasing cholesterol/phospholipid ratio. Vesicle disruption by taurodeoxycholate (3 alpha, 12 alpha-dihydroxy-5 beta-cholanoyl taurine) was reduced in a concentration-dependent manner by addition of tauroursodeoxycholate (3 alpha,7 beta-dihydroxy-5 beta-cholanoyl taurine) (TUDC) when the cholesterol/phospholipid ratio was > or = 0.5, but TUDC was not protective at a cholesterol/phospholipid ratio < or = 0.2. Glycoursodeoxycholate (3 alpha,7 beta-dihydroxy-5 beta-cholanoyl glycine) was somewhat less protective than TUDC, and unconjugated ursodeoxycholate (3 alpha,7 beta-dihydroxy-5 beta-cholanoate) (UDC) had little effect. Taurine conjugates of several other hydrophilic bile salts were also protective, but protection was not strictly proportional to hydrophilicity.
CONCLUSIONS: Conjugates of UDC and other hydrophilic bile salts can reduce disruption of cholesterol-rich model membranes by more toxic bile salts via a purely physicochemical mechanism. UDC conjugates in vivo may protect the cholestatic liver by preventing bile salt disruption of the cholesterol-rich canalicular membrane.

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Year:  1994        PMID: 8174892     DOI: 10.1016/0016-5085(94)90027-2

Source DB:  PubMed          Journal:  Gastroenterology        ISSN: 0016-5085            Impact factor:   22.682


  20 in total

1.  The ursodeoxycholic acid story in primary biliary cirrhosis.

Authors:  A G Lim; R P Jazrawi; T C Northfield
Journal:  Gut       Date:  1995-09       Impact factor: 23.059

2.  Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration.

Authors:  Brian C Oveson; Takeshi Iwase; Sean F Hackett; Sun Young Lee; Shinichi Usui; Thomas W Sedlak; Solomon H Snyder; Peter A Campochiaro; Jennifer U Sung
Journal:  J Neurochem       Date:  2010-12-02       Impact factor: 5.372

Review 3.  Ursodeoxycholic acid treatment of vanishing bile duct syndromes.

Authors:  Thomas Pusl; Ulrich Beuers
Journal:  World J Gastroenterol       Date:  2006-06-14       Impact factor: 5.742

Review 4.  Bile acid interactions with cholangiocytes.

Authors:  Xuefeng Xia; Heather Francis; Shannon Glaser; Gianfranco Alpini; Gene LeSage
Journal:  World J Gastroenterol       Date:  2006-06-14       Impact factor: 5.742

5.  Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis.

Authors:  K D Setchell; C M Rodrigues; M Podda; A Crosignani
Journal:  Gut       Date:  1996-03       Impact factor: 23.059

6.  Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin.

Authors:  Q W Xu; R B Scott; D T Tan; E A Shaffer
Journal:  Gut       Date:  1998-12       Impact factor: 23.059

7.  Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas.

Authors:  W A Faubion; M E Guicciardi; H Miyoshi; S F Bronk; P J Roberts; P A Svingen; S H Kaufmann; G J Gores
Journal:  J Clin Invest       Date:  1999-01       Impact factor: 14.808

8.  Hepatoprotection with tauroursodeoxycholate and beta muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways.

Authors:  P Milkiewicz; M G Roma; E Elias; R Coleman
Journal:  Gut       Date:  2002-07       Impact factor: 23.059

9.  A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.

Authors:  C M Rodrigues; G Fan; X Ma; B T Kren; C J Steer
Journal:  J Clin Invest       Date:  1998-06-15       Impact factor: 14.808

10.  Adjuvant cholylsarcosine during ursodeoxycholic acid treatment of primary biliary cirrhosis.

Authors:  P Ricci; A F Hofmann; L R Hagey; R A Jorgensen; E Rolland Dickson; K D Lindor
Journal:  Dig Dis Sci       Date:  1998-06       Impact factor: 3.199

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