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SHR Neuro Krebs Kardio Lipid

Baghdasaryan, A; Fickert, P; Fuchsbichler, A; Silbert, D; Gumhold, J; Hörl, G; Langner, C; Moustafa, T; Halilbasic, E; Claudel, T; Trauner, M.
Role of hepatic phospholipids in development of liver injury in Mdr2 (Abcb4) knockout mice.
Liver Int. 2008; 28(7):948-958
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Autor/innen der Med Uni Graz:
Baghdasaryan Anna
Claudel Thierry
Fickert Peter
Halilbasic Emina
Hörl Gerd
Langner Cord
Moustafa Tarek
Silbert-Wagner Dagmar
Sommer Judith
Trauner Michael
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Abstract:
Multidrug resistance protein 2 (Abcb4) gene knockout mice (Mdr2(-/-)) lack phosphatidylcholine (PC) excretion into bile and spontaneously develop sclerosing cholangitis, biliary fibrosis and hepatocellular carcinomas. We therefore aimed to test whether formation and hepatic retention of abnormal PC metabolites contribute to the pathogenesis of liver injury in Mdr2(-/-) mice. Mdr2(-/-) mice were either fed a diet supplemented with soybean lecithin 2.5% w/w [phosphatidylcholine-enriched diet (PCD), to increase hepatic PC content] or a choline-deficient diet (CDD, to reduce hepatic PC content) for 4 weeks; controls received chow with energy and nutrient content equivalent to PCD and CDD. Serum liver tests, liver histology, markers of fibrosis, cholangiocyte activation, cell proliferation and thin-layer chromatography for phospholipid (PL) composition were carried out. PCD decreased serum alkaline phosphatase and total bilirubin levels compared with controls, while liver histology as well as hepatic hydroxyproline content as markers of liver fibrosis did not differ among groups. Both PCD and CDD decreased hepatocellular proliferation compared with controls. Hepatic, serum and biliary PLs remained unchanged despite dietary manipulations and no potentially toxic PL metabolites were detected. Mdr2(-/-) mice maintain stable hepatic, serum and biliary PL metabolism in response to dietary PC manipulations. Our findings therefore suggest that liver injury in Mdr2(-/-) mice is not due to formation of toxic PL metabolites.
Find related publications in this database (using NLM MeSH Indexing)
Alkaline Phosphatase - blood
Animals -
Bile - metabolism
Bilirubin - blood
Cell Proliferation - drug effects
Cholestasis, Intrahepatic - chemically induced Cholestasis, Intrahepatic - metabolism Cholestasis, Intrahepatic - pathology
Cholesterol - metabolism
Choline Deficiency - metabolism Choline Deficiency - pathology
Diet -
Disease Models, Animal -
Drug Resistance, Multiple -
Hepatocytes - drug effects Hepatocytes - metabolism Hepatocytes - pathology
Lecithins - administration & dosage Lecithins - metabolism
Liver - drug effects Liver - metabolism Liver - pathology
Liver Function Tests -
Male -
Mice -
Mice, Knockout -
P-Glycoproteins - deficiency P-Glycoproteins - genetics P-Glycoproteins - metabolism

Find related publications in this database (Keywords)
Mdr2
phosphatidylcholine
portal fibrosis
sclerosing cholangitis
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