Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene
| Autor: | Ronald P.J. Oude Elferink, A. K. Groen, M. A. Van den Bergh Weerman, G. J. A. Offerhaus, C. M. J. Van Nieuwkerk, G. N. J. Tytgat, Koert P. Dingemans, Roelof Ottenhoff |
|---|---|
| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
ATP Binding Cassette Transporter Subfamily B Cholangitis medicine.drug_class Administration Oral Gene Expression Mice chemistry.chemical_compound Liver disease Fibrosis Internal medicine medicine Animals Bile Weaning ATP Binding Cassette Transporter Subfamily B Member 1 P-glycoprotein Food Formulated Hepatology biology Bile acid Liver Cirrhosis Biliary Cholesterol Liver Diseases Ursodeoxycholic Acid Gastroenterology Cholic Acids Ursodeoxycholate medicine.disease Drug Resistance Multiple Mice Mutant Strains Endocrinology Liver chemistry Knockout mouse biology.protein ATP-Binding Cassette Transporters Chemical and Drug Induced Liver Injury |
| Zdroj: | Gastroenterology, 111(1), 165-171. W.B. Saunders Ltd |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/gast.1996.v111.pm8698195 |
| Popis: | BACKGROUND & AIMS: The mouse mdr2 gene encodes a P-glycoprotein expressed in the hepatocanalicular membrane. Inactivation of this gene causes lack of biliary phospholipid and cholesterol secretion and non- suppurative cholangitis. The aim of this study was to investigate the role of bile salt hydrophobicity in induction of liver pathology in mdr2 (-/-) mice. METHODS: Mice (+/+) wild type or (-/-) knockout for the mdr2 gene were fed with either purified control diet or this diet supplemented with cholate (0.1%) or ursodeoxycholate (0.5%) for 3, 6, or 22 weeks after weaning. Liver histology was semiquantitatively scored. RESULTS: Each mouse fed bile acid became the major constituent of the bile salt pool. The cholate diet during 22 weeks induced only very mild liver pathology in (+/+) mice. By contrast, lever histology had already deteriorated after 3 weeks in the (-/-) mice and caused pronounced inflammatory nonsuppurative cholangitis and fibrosis in the 75% of mice that survived. Dietary ursodeoxycholate had no effect on histology in (+/+) mice but improved liver pathology significantly in (- /-) mice compared with purified control diet; the decrease of ductular proliferation and portal inflammation was most prominent after 22 weeks. CONCLUSIONS: The cholangiolitis and its sequelae in the mdr2 knockout mice depend on bile salt hydrophobicity. (Gastroenterology 1996 Jul;111(1):165-71) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|