{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:09:50Z","timestamp":1789582190701,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1765,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,11]]},"abstract":"\n \n \n Nor<\/jats:bold>\n UDCA (24<\/jats:bold>\n -\n nor<\/jats:bold>\n ursodeoxycholic acid), the C23-homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic<\/jats:bold>\n Mdr2<\/jats:bold>\n (<\/jats:bold>\n Abcb4<\/jats:bold>\n ) (multidrug resistance protein 2\/ATP-binding cassette b4) knockout mice with sclerosing\/fibrosing cholangitis. In contrast to UDCA,<\/jats:bold>\n nor<\/jats:bold>\n UDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine-conjugated UDCA (C24) and<\/jats:bold>\n nor<\/jats:bold>\n UDCA (C23) in isolated perfused rat liver (IPRL) and in natrium\/taurocholate cotransporting polypeptide (Ntcp)-transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predominantly hepatocellular cholestasis in IPRL. Bile flow was determined gravimetrically; bile acids determined by gas chromatography and liquid chromatography\/tandem mass spectrometry; the Mrp2 model substrate, 2,4-dinitrophenyl-S-glutathione (GS-DNP) was determined spectrophotometrically; and apoptosis was determined immunocytochemically. The choleretic effect of C23-bile acids was comparable to their C24-homologs in IPRL. In contrast, T<\/jats:bold>\n nor<\/jats:bold>\n UDCA, but not<\/jats:bold>\n nor<\/jats:bold>\n UDCA antagonized the cholestatic effect of TLCA. Bile flow (percent of controls) was 8% with TLCA-induced cholestasis, and unchanged by coinfusion of<\/jats:bold>\n nor<\/jats:bold>\n UDCA (14%). However, it was increased by T<\/jats:bold>\n nor<\/jats:bold>\n UDCA (83%), UDCA (73%) and TUDCA (136%). Secretion of GS-DNP was markedly reduced by TLCA (5%), unimproved by<\/jats:bold>\n nor<\/jats:bold>\n UDCA (4%) or UDCA (17%), but was improved modestly by T<\/jats:bold>\n nor<\/jats:bold>\n UDCA (26%) or TUDCA (58%). No apoptosis was observed in IPRL exposed to low micromolar TLCA, but equivalent antiapoptotic effects of TUDCA and T<\/jats:bold>\n nor<\/jats:bold>\n UDCA were observed in Ntcp-HepG2 cells exposed to TLCA.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Conjugation is essential for the anticholestatic effect of<\/jats:bold>\n nor<\/jats:bold>\n UDCA in a model of hepatocellular cholestasis. Combined therapy with UDCA and<\/jats:bold>\n nor<\/jats:bold>\n UDCA may be superior to UDCA or<\/jats:bold>\n nor<\/jats:bold>\n UDCA monotherapy in biliary disorders in which hepatocyte as well as cholangiocyte dysfunction contribute to disease progression. (Hepatology 2010;52:1758-1768)<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.23911","type":"journal-article","created":{"date-parts":[[2010,8,22]],"date-time":"2010-08-22T08:11:40Z","timestamp":1282464700000},"page":"1758-1768","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":43,"title":["Conjugation Is Essential for the Anticholestatic Effect of Nor Ursodeoxycholic Acid in Taurolithocholic Acid\u2013Induced Cholestasis in Rat Liver"],"prefix":"10.1097","volume":"52","author":[{"given":"Gerald 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