Document Detail

Role of bile acids in liver injury and regeneration following acetaminophen overdose.
MedLine Citation:
PMID:  24007882     Owner:  NLM     Status:  MEDLINE    
Bile acids play a critical role in liver injury and regeneration, but their role in acetaminophen (APAP)-induced liver injury is not known. We tested the effect of bile acid modulation on APAP hepatotoxicity using C57BL/6 mice, which were fed a normal diet, a 2% cholestyramine (CSA)-containing diet for bile acid depletion, or a 0.2% cholic acid (CA)-containing diet for 1 week before treatment with 400 mg/kg APAP. CSA-mediated bile acid depletion resulted in significantly higher liver injury and delayed regeneration after APAP treatment. In contrast, 0.2% CA supplementation in the diet resulted in a moderate delay in progression of liver injury and significantly higher liver regeneration after APAP treatment. Either CSA-mediated bile acid depletion or CA supplementation did not affect hepatic CYP2E1 levels or glutathione depletion after APAP treatment. CSA-fed mice exhibited significantly higher activation of c-Jun N-terminal protein kinases and a significant decrease in intestinal fibroblast growth factor 15 mRNA after APAP treatment. In contrast, mice fed a 0.2% CA diet had significantly lower c-Jun N-terminal protein kinase activation and 12-fold higher fibroblast growth factor 15 mRNA in the intestines. Liver regeneration after APAP treatment was significantly faster in CA diet-fed mice after APAP administration secondary to rapid cyclin D1 induction. Taken together, these data indicate that bile acids play a critical role in both initiation and recovery of APAP-induced liver injury.
Bharat Bhushan; Prachi Borude; Genea Edwards; Chad Walesky; Joshua Cleveland; Feng Li; Xiaochao Ma; Udayan Apte
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-09-03
Journal Detail:
Title:  The American journal of pathology     Volume:  183     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-10-28     Completed Date:  2014-06-10     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1518-26     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Acetaminophen / adverse effects*
Bile Acids and Salts / metabolism*
Cholestyramine Resin / pharmacology
Drug Overdose / pathology*,  physiopathology*
Drug-Induced Liver Injury / genetics,  pathology*,  physiopathology*
Feeding Behavior / drug effects
Fibroblast Growth Factors / genetics,  metabolism
Gene Expression Regulation / drug effects
Intestines / drug effects,  metabolism,  pathology
Liver / drug effects,  metabolism,  pathology
Liver Regeneration* / drug effects,  genetics
Mice, Inbred C57BL
RNA, Messenger / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; 0/RNA, Messenger; 0/fibroblast growth factor 15, mouse; 11041-12-6/Cholestyramine Resin; 362O9ITL9D/Acetaminophen; 62031-54-3/Fibroblast Growth Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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