Intestinal permeability in the pathogenesis of NSAID-induced enteropathy

Abstract

NSAID enteropathy is associated with significant morbidity and occasionally mortality. There are no proven effective ways of preventing this damage. Because increased intestinal permeability appears to be a central mechanism in the pathogenesis of NSAID enteropathy, it becomes a potential therapeutic target for prevention. At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of NSAID enteropathy.

Meloxicam-induced enteropathy of the small bowel

“…5 Reduction in gastric acid secretion does not play an important role in prevention. 1 As noted in our patient, concurrent use of omeprazole did not prevent the NSAID-induced enteropathy.…”

“…1 NSAIDs uncouple mitochondrial oxidative phosphorylation, which reduces the intracellular levels of adenosine triphosphate in the enterocyte. This in turn reduces the integrity of intercellular junctions and increases intestinal permeability.…”

“…The development of ulcers and the subsequent reparative process is thought to result in diaphragm-like strictures. 1,2 Prostaglandin synthesis from arachidonic acid by the damaged cells is decreased secondary to the inhibition of cyclo-oxygenase (COX) by NSAIDs. This effect further increases the damage caused by the inflammatory response.…”

“…9 Even though long-term concurrent use of misoprostol may not prevent the development of enteropathy, it does reduce intestinal inflammation in patients with established NSAIDinduced enteropathy and lessens the severity of the disease. 1 The reduction in intestinal inflammation and blood loss reported with the use of metronidazole has been attributed to the antibacterial properties of the drug and the role of bacterial invasion in NSAID-induced enteropathy. 10 Another probable mechanism underlying the protective effect of metronidazole is the reduction in the degree of uncoupling of mitochondrial oxidative phosphorylation induced by NSAIDs.…”

“…10 Another probable mechanism underlying the protective effect of metronidazole is the reduction in the degree of uncoupling of mitochondrial oxidative phosphorylation induced by NSAIDs. 1 Sulfasalazine is another drug reported to reduce intestinal inflammation and blood loss. 1,2 However, these results were from small pilot studies and require careful interpretation.…”