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Anti-oxidants do not prevent bile acid-induced cell death in rat hepatocytes.
MedLine Citation:
PMID:  20825559     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Bile acids, reactive oxygen species (ROS) and inflammatory cytokines are crucial regulators of cell death in acute and chronic liver diseases. The contribution of each factor to hepatocyte death, either apoptosis or necrosis, has not been clarified as yet. It has been suggested that the generation of oxidative stress by bile acids contributes to hepatocyte death during cholestasis and bile acid toxicity, although the beneficial role of ROS prevention in bile acid-mediated cell death is not fully understood.
AIM: Study the effects of anti-oxidants in bile acid-induced cell death in vitro.
METHODS: Primary rat hepatocytes were exposed to the bile acids glycochenodeoxycholic acid (GCDCA) or taurolithocholic acid-3 sulphate in the absence or presence of ROS scavengers or anti-oxidants. Haeme oxygenase (HO)-1 mRNA levels were analysed by quantitative polymerase chain reaction. Apoptosis was quantified by acridine orange staining and caspase-3 activity assay. Necrosis was detected by Sytox green staining.
RESULTS: Anti-oxidants do not attenuate bile acid-induced cell death. Furthermore, bile acid exposure does not enhance the mRNA expression of the oxidative stress-responsive gene HO-1. The Src-kinase inhibitor, SU6656, does reduce GCDCA-induced apoptosis and necrosis.
CONCLUSIONS: In hepatocytes, bile acid-induced toxicity is not prevented by scavengers of oxidative stress. The beneficial effects observed in patients might be because of the contribution of ROS and cytokines rather than bile acid-mediated oxidative stress. However, the use of specific Src kinase inhibitors might be a useful tool to prevent bile acid-induced injury in liver diseases.
Authors:
Titia E Woudenberg-Vrenken; Manon Buist-Homan; Laura Conde de la Rosa; Klaas Nico Faber; Han Moshage
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-02
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  30     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  1511-21     Citation Subset:  IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
Affiliation:
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
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Comment In:
Liver Int. 2011 Feb;31(2):273-4; author reply 274-5   [PMID:  21073650 ]

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