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Updated: Aug 21, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Mechanisms underlying intestinal injury induced by anti-inflammatory COX inhibitors
1William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine, Charterhouse Square, London, EC1M 6BQ, England. b.j.whittle@qmul.ac.uk
Abstract:
By far the most attention has been paid to the deleterious actions of nonsteroidal anti-inflammatory drugs (NSAIDs), including isoform selective agents that inhibit cyclooxygenase (COX), on the upper gastrointestinal tract, particularly the gastric and duodenal mucosa. However, recent studies confirm a relatively high incidence of serious clinical events, especially with the more-established drugs of this class, involving the small intestine. Pathogenic factors that have been proposed from early studies in such enteropathy have included the enterohepatic circulation of the nonsteroidal anti-inflammatory drugs, inhibition of cyclooxygenase, surface epithelial changes and focal microvascular events. More recent work has concerned the role of infiltrating inflammatory cells, the relative roles of cyclooxygenase isoforms, COX-1 and COX-2 and the key involvement of inducible nitric oxide (NO) synthase and its product in combination with superoxide, peroxynitrite. In the present review, evidence for the underlying involvement of each these processes, and their sequential integration in the development of the intestinal injury and ulceration promoted by nonsteroidal anti-inflammatory drugs has been considered.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause significant small intestine damage through cyclooxygenase (COX) inhibition and inflammatory pathways. Understanding these mechanisms is crucial for managing NSAID-induced enteropathy and its serious clinical events.
Area of Science:
- Gastroenterology
- Pharmacology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation.
- While upper gastrointestinal effects are well-documented, NSAIDs also cause significant small intestinal injury (enteropathy).
- Established NSAIDs are associated with a high incidence of serious clinical events in the small intestine.
Purpose of the Study:
- To review the pathogenic factors contributing to NSAID-induced enteropathy.
- To examine the sequential integration of these processes in the development of intestinal injury.
Main Methods:
- Review of existing literature on NSAID enteropathy.
- Analysis of proposed pathogenic factors including enterohepatic circulation, COX inhibition, epithelial changes, microvascular events, inflammatory cells, and nitric oxide pathways.
Main Results:
- NSAID enteropathy involves multiple integrated mechanisms.
- Key factors include cyclooxygenase (COX) isoform inhibition (COX-1 and COX-2), enterohepatic circulation, and epithelial damage.
- Inducible nitric oxide (NO) synthase and its product peroxynitrite play a critical role in mediating injury.
Conclusions:
- NSAID-induced intestinal injury is a complex process involving multiple interacting pathways.
- Understanding these mechanisms is essential for developing strategies to prevent and treat NSAID enteropathy.
- Further research into the specific roles of COX isoforms and NO pathways may lead to safer NSAID use.
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