Document Detail


Reduction of gastrointestinal injury in acute endotoxic shock by flurbiprofen nitroxybutylester.
MedLine Citation:
PMID:  7498255     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitric oxide has been reported to have paradoxical effects in experimental endotoxic shock, contributing to the hemodynamic consequences of endotoxin administration, but apparently protecting the gastrointestinal mucosa. A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent nonsteroidal anti-inflammatory drugs from which they are derived. Thus, the present study was performed to determine the effects of one of these derivatives, flurbiprofen 4-nitroxybutylester, compared to the native nonsteroidal anti-inflammatory drug, flurbiprofen, in an experimental model of endotoxic shock. Intravenous administration of endotoxin from Salmonella typhosa to rats pretreated with flurbiprofen produced a profound decrease in systemic arterial blood pressure, an increase in hematocrit and extensive gastric and small intestinal damage. In rats pretreated with flurbiprofen 4-nitroxybutylester, endotoxin produced comparable changes in blood pressure and hematocrit to those seen in rats treated with flurbiprofen; however, the severity of gastrointestinal damage was significantly reduced. Gastric blood flow was profoundly decreased following endotoxin administration, but was significantly higher in rats pretreated with flurbiprofen 4-nitroxybutylester than in rats pretreated with flurbiprofen. These results demonstrate that despite not affecting the acute systemic effects of endotoxin administration, flurbiprofen 4-nitroxybutylester is capable of protecting the gastrointestinal mucosa from injury, possibly through preservation of mucosal blood flow.
Authors:
J L Wallace; G Cirino; G W McKnight; S N Elliott
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  280     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1996-01-18     Completed Date:  1996-01-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  63-8     Citation Subset:  IM    
Affiliation:
Intestinal Disease Research Unit, Faculty of Medicine, University of Calgary, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
Blood Pressure / drug effects
Flurbiprofen / therapeutic use
Gastric Mucosa / drug effects
Gastrointestinal Diseases / chemically induced,  prevention & control*
Gastrointestinal Hemorrhage / chemically induced,  prevention & control
Lipopolysaccharides / toxicity
Male
Nitric Oxide / physiology
Rats
Rats, Sprague-Dawley
Salmonella typhi
Shock, Septic / complications*,  drug therapy*
Stomach / blood supply
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Lipopolysaccharides; 10102-43-9/Nitric Oxide; 5104-49-4/Flurbiprofen

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


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