PMID- 21707612
OWN - NLM
STAT- MEDLINE
DCOM- 20120419
LR  - 20131121
IS  - 1365-2362 (Electronic)
IS  - 0014-2972 (Linking)
VI  - 42
IP  - 2
DP  - 2012 Feb
TI  - Comparison of different bile acid-phospholipid conjugates in acute hepatitis.
PG  - 130-8
LID - 10.1111/j.1365-2362.2011.02563.x [doi]
AB  - INTRODUCTION: The bile acid-phospholipid conjugate ursodeoxycholyl 
      lysophosphatidylethanolamide (UDCA-LPE) is a promising novel compound with 
      profound hepatoprotective functions in vitro and in vivo. Because of high costs 
      of LPE synthesis from hydrolysis of phosphatidylethanolamide (PE), costs for 
      UDCA-LPE synthesis for in vivo and human use can become quite high. In this 
      study, we evaluated whether ursodeoxycholyl phosphatidylethanolamide (udca-pe), 
      which is more cost-effective, could replace udca-lpe in terms of protection from 
      hepatocellular injury. MATERIALS AND METHODS: Anti-apoptotic and 
      anti-inflammatory properties of UDCA-PE and UDCA-LPE were compared in 
      TNFalpha/cyclohexamide (CHX)-treated HepG2 cells as well as in a mouse model of 
      d-galactosamine/lipopolysaccharide (Gal/LPS)-induced acute liver injury. RESULTS: 
      Ursodeoxycholyl lysophosphatidylethanolamide inhibited TNFalpha/CHX-induced apoptosis 
      in HepG2 cells in a dose-dependent manner and markedly ameliorated 
      Gal/LPS-mediated fulminant hepatitis in mice. In contrast, UDCA-PE showed weaker 
      hepatoprotective functions at low concentrations, and protection was lost at 
      higher dosage. Analysis of hepatic gene expression showed that both conjugates 
      significantly reduced Gal/LPS-mediated expression of chemoattractants, such as 
      monocyte chemotactic protein 1 (MCP1) and RANTES. These inhibitory effects by 
      UDCA-PE were transient while those by UDCA-LPE were sustained in attenuating 
      expression of inflammatory MCP1 and RANTES expression. CONCLUSIONS: Our data 
      underline the superiority of UDCA-LPE compared to UDCA-PE in ameliorating acute 
      liver inflammation. This indicates the significance of the lyso-functional group 
      of bile acid conjugate for optimal hepatoprotection and reduction in inflammation 
      in vivo.
CI  - (c) 2011 The Authors. European Journal of Clinical Investigation (c) 2011 Stichting 
      European Society for Clinical Investigation Journal Foundation.
FAU - Pathil, Anita
AU  - Pathil A
AD  - Department of Internal Medicine IV, Gastroenterology and Hepatology, University 
      of Heidelberg, Heidelberg, Germany.
FAU - Warth, Arne
AU  - Warth A
FAU - Chamulitrat, Walee
AU  - Chamulitrat W
FAU - Stremmel, Wolfgang
AU  - Stremmel W
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110627
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Cholagogues and Choleretics)
RN  - 0 (Lysophospholipids)
RN  - 724L30Y2QR (Ursodeoxycholic Acid)
SB  - IM
MH  - Animals
MH  - Bile/drug effects
MH  - Cell Line, Tumor
MH  - Cholagogues and Choleretics/*pharmacology
MH  - Flow Cytometry
MH  - Gene Expression/drug effects
MH  - Hepatitis/*drug therapy
MH  - Humans
MH  - Liver/drug effects
MH  - Lysophospholipids/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microarray Analysis
MH  - Models, Animal
MH  - Real-Time Polymerase Chain Reaction
MH  - Ursodeoxycholic Acid/*pharmacology
EDAT- 2011/06/29 06:00
MHDA- 2012/04/20 06:00
CRDT- 2011/06/29 06:00
PHST- 2011/06/29 06:00 [entrez]
PHST- 2011/06/29 06:00 [pubmed]
PHST- 2012/04/20 06:00 [medline]
AID - 10.1111/j.1365-2362.2011.02563.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2012 Feb;42(2):130-8. doi: 10.1111/j.1365-2362.2011.02563.x. 
      Epub 2011 Jun 27.