{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:36:39Z","timestamp":1790285799001,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Bile duct ligation (BDL) is an experimental procedure that mimics obstructive cholestatic disease. One of the early consequences of BDL in rodents is the appearance of so\u2010called bile infarcts that correspond to Charcot\u2010Gombault necrosis in human cholestasis. The mechanisms causing bile infarcts and their pathophysiological relevance are unclear. Therefore, intravital two photon\u2013based imaging of BDL mice was performed with fluorescent bile salts (BS) and non\u2010BS organic anion analogues. Key findings were followed up by matrix\u2010assisted laser desorption ionization imaging, clinical chemistry, immunostaining, and gene expression analyses. In the acute phase, 1\u20103 days after BDL, BS concentrations in bile increased and single\u2010cell bile microinfarcts occurred in dispersed hepatocytes throughout the liver caused by the rupture of the apical hepatocyte membrane. This rupture occurred after loss of mitochondrial membrane potential, followed by entry of bile, cell death, and a \u201cdomino effect\u201d of further death events of neighboring hepatocytes. Bile infarcts provided a trans\u2010epithelial shunt between bile canaliculi and sinusoids by which bile constituents leaked into blood. In the chronic phase, \u226521 days after BDL, uptake of BS tracers at the sinusoidal hepatocyte membrane was reduced. This contributes to elevated concentrations of BS in blood and decreased concentrations in the biliary tract. <jats:bold>Conclusion:\n                           <\/jats:bold> Bile microinfarcts occur in the acute phase after BDL in a limited number of dispersed hepatocytes followed by larger infarcts involving neighboring hepatocytes, and they allow leakage of bile from the BS\u2010overloaded biliary tract into blood, thereby protecting the liver from BS toxicity; in the chronic phase after BDL, reduced sinusoidal BS uptake is a dominant protective factor, and the kidney contributes to the elimination of BS until cholemic nephropathy sets in.<\/jats:p>","DOI":"10.1002\/hep.30213","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T15:30:22Z","timestamp":1534174222000},"page":"666-683","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":89,"title":["Bile Microinfarcts in Cholestasis Are Initiated by Rupture of the Apical Hepatocyte Membrane and Cause Shunting of Bile to Sinusoidal Blood"],"prefix":"10.1097","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0695-3403","authenticated-orcid":false,"given":"Ahmed","family":"Ghallab","sequence":"first","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund,Dortmund,Germany"},{"name":"Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine,South Valley University,Qena,Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology and University of T\u00fcbingen,Stuttgart,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selahaddin","family":"Sezgin","sequence":"additional","affiliation":[{"name":"Institute of Environmental Research, Department of 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Dortmund,Dortmund,Germany"},{"name":"Institute National de Recherche en Informatique et en Automatique,Le Chesnay,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Godoy","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund,Dortmund,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Markus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Medicine III,University Hospital RWTH Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Guenther","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund,Dortmund,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Veterinary Medicine,South Valley University,Qena,Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya A.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine,South Valley University,Qena,Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Keitel","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases,University Hospital D\u00fcsseldorf, Medical Faculty at Heinrich\u2010Heine\u2010University,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Kuepfer","sequence":"additional","affiliation":[{"name":"Systems Pharmacology,Bayer AG,Leverkusen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Dooley","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Medical Faculty Mannheim,Heidelberg University,Mannheim,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[{"name":"Department of Medicine II,Saarland University Medical Center, Saarland University,Homburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Medicine III,University Hospital RWTH Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Spiteller","sequence":"additional","affiliation":[{"name":"Institute of Environmental Research, Department of Chemistry and Chemical Biology,Technical University Dortmund 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