Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene

C. M J Van Nieuwkerk, R. P J O Elferink, A. K. Groen, R. Ottenhoff, G. N J Tytgat, K. P. Dingemans, M. A. Van den Bergh Weerman, G. J A Offerhaus

Research output: Contribution to journalArticle

Abstract

Background and 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 chelate diet during 22 weeks induced only very mild liver pathology in (+/+) mice. By contrast, liver 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.

Original languageEnglish (US)
Pages (from-to)165-171
Number of pages7
JournalGastroenterology
Volume111
Issue number1
DOIs
StatePublished - 1996
Externally publishedYes

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Cholates
P-Glycoprotein
Liver Diseases
Genes
Bile Acids and Salts
Liver
Diet
Histology
Cholangitis
Pathology
Hydrophobic and Hydrophilic Interactions
Gene Knockout Techniques
Gene Silencing
Weaning
Knockout Mice
Phospholipids
Fibrosis
Cholesterol
Inflammation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Van Nieuwkerk, C. M. J., Elferink, R. P. J. O., Groen, A. K., Ottenhoff, R., Tytgat, G. N. J., Dingemans, K. P., ... Offerhaus, G. J. A. (1996). Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology, 111(1), 165-171. https://doi.org/10.1053/gast.1996.v111.pm8698195

Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. / Van Nieuwkerk, C. M J; Elferink, R. P J O; Groen, A. K.; Ottenhoff, R.; Tytgat, G. N J; Dingemans, K. P.; Van den Bergh Weerman, M. A.; Offerhaus, G. J A.

In: Gastroenterology, Vol. 111, No. 1, 1996, p. 165-171.

Research output: Contribution to journalArticle

Van Nieuwkerk, CMJ, Elferink, RPJO, Groen, AK, Ottenhoff, R, Tytgat, GNJ, Dingemans, KP, Van den Bergh Weerman, MA & Offerhaus, GJA 1996, 'Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene', Gastroenterology, vol. 111, no. 1, pp. 165-171. https://doi.org/10.1053/gast.1996.v111.pm8698195
Van Nieuwkerk, C. M J ; Elferink, R. P J O ; Groen, A. K. ; Ottenhoff, R. ; Tytgat, G. N J ; Dingemans, K. P. ; Van den Bergh Weerman, M. A. ; Offerhaus, G. J A. / Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. In: Gastroenterology. 1996 ; Vol. 111, No. 1. pp. 165-171.
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AU - Dingemans, K. P.

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