| Reduction of gastrointestinal injury in acute endotoxic shock by flurbiprofen nitroxybutylester. | |
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MedLine Citation:
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PMID: 7498255 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J L Wallace; G Cirino; G W McKnight; S N Elliott |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 280 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 1995 Jun |
Date Detail:
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Created Date: 1996-01-18 Completed Date: 1996-01-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 63-8 Citation Subset: IM |
Affiliation:
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Intestinal Disease Research Unit, Faculty of Medicine, University of Calgary, Alberta, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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