Document Detail


Novel insight into mechanisms of cholestatic liver injury.
MedLine Citation:
PMID:  23049206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholestasis results in a buildup of bile acids in serum and in hepatocytes. Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acid-induced apoptosis as the major cause of hepatocellular injury. Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology. Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum, liver, and bile to very low levels of detection. Interestingly, toxic bile acid levels are seemingly far lower than previously hypothesized. The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture, the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury. This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis, and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis, but may involve largely inflammatory cell-mediated liver cell necrosis.
Authors:
Benjamin L Woolbright; Hartmut Jaeschke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-10     Completed Date:  2013-05-03     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  4985-93     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Bile Acids and Salts / analysis,  toxicity*
Cholestasis / pathology*
Glycochenodeoxycholic Acid / toxicity
Hepatocytes / pathology*
Humans
Ligation
Necrosis
Signal Transduction
Grant Support
ID/Acronym/Agency:
R01 AA12916/AA/NIAAA NIH HHS; R01 DK070195/DK/NIDDK NIH HHS; T32 ES007079-26A2/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 640-79-9/Glycochenodeoxycholic Acid
Comments/Corrections

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