Document Detail

Acetaminophen hepatotoxicity: NO to the rescue.
MedLine Citation:
PMID:  15345657     Owner:  NLM     Status:  MEDLINE    
Severe liver injury as a result of overdose or chronic use of acetaminophen (paracetamol) remains a significant clinical problem, accounting for as much as 40% of cases of acute liver failure. The mechanisms underlying the liver injury caused by acetaminophen have become much better understood in recent years. In this issue, Fiorucci et al. report that delivery of nitric oxide (NO) in small amounts to the liver, via a novel derivative of the bile acid ursodeoxycholic acid, results in significant protection of the liver from acetaminophen-induced damage. NO appears to produce these beneficial actions through several mechanisms, including the suppression of synthesis of several proinflammatory cytokines. There is also substantial evidence that a NO-releasing derivative of acetaminophen offers several advantages over acetaminophen itself, including enhanced analgesic potency and reduced liver toxicity.
John L Wallace
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Publication Detail:
Type:  Comment; Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  143     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-03     Completed Date:  2005-02-09     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-2     Citation Subset:  IM    
Department of Pharmacology & Therapeutics, Mucosal Inflammation Research Group, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
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MeSH Terms
Acetaminophen / pharmacokinetics,  toxicity*
Analgesics, Non-Narcotic / pharmacokinetics,  toxicity*
Dose-Response Relationship, Drug
Drug-Induced Liver Injury / pathology,  prevention & control*
Liver / pathology
Nitrates / therapeutic use*
Nitric Oxide / therapeutic use*
Nitric Oxide Donors / therapeutic use*
Ursodeoxycholic Acid / analogs & derivatives*,  therapeutic use*
Reg. No./Substance:
0/2-methyl-3-(2-((4-nitrooxybutyloxy)carbonyl)vinyl)phenyl ursodeoxycholic acid ester; 0/Analgesics, Non-Narcotic; 0/Nitrates; 0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 103-90-2/Acetaminophen; 128-13-2/Ursodeoxycholic Acid
Comment On:
Br J Pharmacol. 2004 Sep;143(1):33-42   [PMID:  15345658 ]

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