The synthetic bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide suppresses TNFα-induced liver injury

• Verfasst von: Pathil-Warth, Anita [VerfasserIn]
• Verfasst von: Warth, Arne [VerfasserIn]
• Verfasst von: Chamulitrat, Walee [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Titel: The synthetic bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide suppresses TNFα-induced liver injury
• Verf.angabe: Anita Pathil, Arne Warth, Walee Chamulitrat, Wolfgang Stremmel
• Jahr: 2011
• Umfang: 11 S.
• Fussnoten: Available online 27 September 2010 ; Gesehen am 23.09.2022
• Titel Quelle: Enthalten in: Journal of hepatology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1985
• Jahr Quelle: 2011
• Band/Heft Quelle: 54(2011), 4, Seite 674-684
• ISSN Quelle: 1600-0641
• DOI: doi:10.1016/j.jhep.2010.07.028
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Erscheint auch als : Druck-Ausgabe: Pathil-Warth, Anita, 1981 - : The synthetic bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide suppresses TNFα-induced liver injury. - 2011
• Sach-SW: Animals
• Sach-SW: Apoptosis
• Sach-SW: Cell Line
• Sach-SW: Chemical and Drug Induced Liver Injury
• Sach-SW: Cholagogues and Choleretics
• Sach-SW: Cytokines
• Sach-SW: Galactosamine
• Sach-SW: Gene Expression
• Sach-SW: Humans
• Sach-SW: Inflammation Mediators
• Sach-SW: Lipopolysaccharides
• Sach-SW: Lysophospholipids
• Sach-SW: Male
• Sach-SW: Mice
• Sach-SW: Mice, Inbred C57BL
• Sach-SW: Phosphatidylcholines
• Sach-SW: Phospholipases A2
• Sach-SW: Phospholipids
• Sach-SW: Tumor Necrosis Factor-alpha
• Sach-SW: Ursodeoxycholic Acid
• K10plus-PPN: 1817340107

Abstract

BACKGROUND & AIMS: Excessive apoptosis and leukocyte-dependent inflammation mediated by pro-inflammatory cytokines, such as TNFα, are cardinal features of acute liver injury. This study evaluated the ability of the newly designed bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) to protect from hepatocellular injury in comparison to the known hepatoprotectant ursodeoxycholic acid (UDCA) and phosphatidylcholine (PC). - METHODS: Anti-apoptotic and anti-inflammatory properties of UDCA-LPE were evaluated after TNFα treatment of embryonic human hepatocyte cell line CL48 as well as of primary human hepatocytes. Acute liver injury was induced in C57BL/6 mice with d-galactosamine/lipopolysaccharide (GalN/LPS) in order to determine in vivo efficacy of the conjugate. - RESULTS: UDCA-LPE inhibited TNFα-induced apoptosis and inflammation in hepatocytes in vitro and markedly ameliorated GalN/LPS-mediated fulminant hepatitis in mice, whereas UDCA or PC failed to show protection. The conjugate was able to decrease injury-induced elevation of phospholipase A(2) activity as well as its product lysophosphatidylcholine. Analysis of hepatic gene expression showed that UDCA-LPE treatment led to favourable inhibitory effects on expression profiles of key pro-inflammatory cytokines and chemokines, which are crucial for leukocyte recruitment and activation thereby inhibiting chemokine-mediated aggravation of parenchymal damage. - CONCLUSIONS: Thus, UDCA-LPE as a synthetic bile acid-phospholipid conjugate may represent a potent anti-inflammatory agent that is more effective than UDCA and PC for treatment of liver diseases.