E-resources
-
Ghallab, Ahmed; Hofmann, Ute; Sezgin, Selahaddin; Vartak, Nachiket; Hassan, Reham; Zaza, Ayham; Godoy, Patricio; Schneider, Kai Markus; Guenther, Georgia; Ahmed, Yasser A.; Abbas, Aya A.; Keitel, Verena; Kuepfer, Lars; Dooley, Steven; Lammert, Frank; Trautwein, Christian; Spiteller, Michael; Drasdo, Dirk; Hofmann, Alan F.; Jansen, Peter L.M.; Hengstler, Jan G.; Reif, Raymond
Hepatology, February 2019, Volume: 69, Issue: 2Journal Article
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‐called bile infarcts that correspond to Charcot‐Gombault necrosis in human cholestasis. The mechanisms causing bile infarcts and their pathophysiological relevance are unclear. Therefore, intravital two photon–based imaging of BDL mice was performed with fluorescent bile salts (BS) and non‐BS organic anion analogues. Key findings were followed up by matrix‐assisted laser desorption ionization imaging, clinical chemistry, immunostaining, and gene expression analyses. In the acute phase, 1‐3 days after BDL, BS concentrations in bile increased and single‐cell 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 “domino effect” of further death events of neighboring hepatocytes. Bile infarcts provided a trans‐epithelial shunt between bile canaliculi and sinusoids by which bile constituents leaked into blood. In the chronic phase, ≥21 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. Conclusion: 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‐overloaded 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.
Author
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.