title: Comparison of different bile acid-phospholipid conjugates in acute hepatitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Anti-apoptotic and anti-inflammatory properties of UDCA-PE and UDCA-LPE were compared in TNFα/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 TNFα/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.
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Walee
authors.initials: W
authors.lastname: Chamulitrat
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D000818:Animals; D001646:Bile / Q000187:drug effects; D045744:Cell Line, Tumor; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006505:Hepatitis / Q000188:drug therapy*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D023421:Models, Animal; D060888:Real-Time Polymerase Chain Reaction; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D002756:Cholagogues and Choleretics; D008246:Lysophospholipids; D014580:Ursodeoxycholic Acid