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Direct toxicity of <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s is currently the most accepted hypothesis for cholestatic liver injury. However, information on which bile acids are actually accumulating during cholestasis is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To assess the <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> composition in liver and serum after bile duct ligation (<jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content>) in male C57Bl\/6 mice between 6\u00a0h and 14\u00a0days and evaluate toxicity of the most abundant <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bile acid concentrations increased in liver (27\u2010fold) and serum (1400\u2010fold) within 6\u00a0h after surgery and remained elevated up to 14\u00a0days. <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s in livers of <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> mice became more hydrophilic than sham controls, mainly because of increased 6\u03b2\u2010hydroxylation and taurine conjugation. Among the eight unconjugated and 16 conjugated <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s identified in serum and liver, only taurocholic acid (<jats:styled-content style=\"fixed-case\">TCA<\/jats:styled-content>), \u03b2\u2010muricholic acid (\u03b2<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content>) and T\u03b2<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content> were substantially elevated representing &gt;95% of these <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s over the entire time course. Although glycochenodeoxycholic acid and other conjugated <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s increased in <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> animals, the changes were several orders of magnitude lower compared with <jats:styled-content style=\"fixed-case\">TCA<\/jats:styled-content>, \u03b2<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content> and T\u03b2<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content>. A mixture of these <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s did not cause apoptosis or necrosis, but induced inflammatory gene expression in cultured murine hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The concentrations of cytotoxic <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s are insufficient to cause hepatocellular injury. In contrast, <jats:styled-content style=\"fixed-case\">TCA<\/jats:styled-content>, \u03b2<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content> and T\u03b2<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content> are able to induce pro\u2010inflammatory mediators in hepatocytes. Thus, <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>s act as inflammagens and not as cytotoxic mediators after <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> in mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02662.x","type":"journal-article","created":{"date-parts":[[2011,10,17]],"date-time":"2011-10-17T05:44:44Z","timestamp":1318830284000},"page":"58-69","source":"Crossref","is-referenced-by-count":173,"title":["Effect of bile duct ligation on bile acid composition in mouse serum and liver"],"prefix":"10.1111","volume":"32","author":[{"given":"Youcai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Young","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University 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