Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine.

Abstract

SUMMARY Intestinal permeability was estimated in healthy subjects after ingestion of aspirin (1.2+1*2 g), ibuprofen (400+400 mg) and indomethacin (75+50 mg) at midnight and an hour before starting a 51chromium labelled ethylenediaminetetraacetate absorption test. Intestinal permeability increased significantly from control levels following each drug and the effect was related to drug potency to inhibit cyclooxygenase. Intestinal permeability increased to a similar extent after oral and rectal administration of indomethacin showing that the effect is systemically mediated. Prostaglandin E2 decreased intestinal permeability significantly but failed to prevent the indomethacin induced increased intestinal permeability. These studies show that non-steroidal anti-inflammatory drugs disrupt the intestinal barrier function in man and suggest that the morphological correlates of the damage may reside at the level of the intercellular junctions.Several non-steroidal anti-inflammatory drugs (NSAIDs) induced characteristic intestinal damage in various animal species.' This is particularly severe in the rat where subcutaneous indomethacin leads to small bowel inflammation with ulceration, perforation, and ultimately death within 72 hours. 5 The precise mechanism underlying this sequence of events is unknown but there is substantial data to implicate both reduced synthesis of mucosal prostaglandings and the presence of intestinal bacteria in the pathogenesis of the lesions.6 7 Thus the macroscopic damage is preceded by a period of profound inhibition of mucosal cyclooxygenase activity8 and damage can be prevented by the simultaneous administration of a variety of prostaglandins.5 9 10 The role of intestinal bacteria is suggested by findings that intestinal ulceration after NSAIDs is rarely seen in germ free animals and the damage is greatly reduced after the coadministration of various antibiotics by a mechanism which appears to differ from their 'cytoprotective' properties. 112Until recently the human small intestine was thought to be relatively unaffected by NSAIDs.

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

“…It is well established that the administration of indomethacin in dosages comparable to that used in the present study increases small intestinal permeability about 2-3 fold (Bjarnason et al, 1986(Bjarnason et al, , 1989(Bjarnason et al, , 1993, which is in line with our results. Intestinal permeability after taking indomethacin for 7 days reverts back to normal within 1 week (Bjarnason et al, 1991).…”

“…An increase in intestinal permeability or a decrease in intestinal barrier function is regarded as a pathophysiological factor in Crohn's disease (Meddings, 1997), celiac disease (Smecuol et al, 1997), viral gastroenteritis (Isolauri et al, 1989) and food allergy (Crowe & Perdue, 1992). Shortly after the administration of indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), small intestinal permeability is increased in the same order of magnitude as in these disorders (Bjarnason et al, 1986). In the present study, we administered indomethacin to healthy volunteers as a model for the gastroenteropathy associated with a rise in small intestinal permeability.…”

Effects of Capsaicin on Cellular Damage and Monolayer Permeability in Human Intestinal Caco-2 Cells

“…Recent studies have suggested that altered intestinal epithelial TJ permeability may be a significant risk factor for many diseases such as Crohn's disease, 3) NSAID-associated enteritis, 22) and diarrheal syndromes. 23) It has been reported that in these disorders, increase in intestinal epithelial TJ permeability allows paracellular penetration of toxic luminal substances, aggravating intestinal inflammation and mucosal injury.…”

“…23) It has been reported that in these disorders, increase in intestinal epithelial TJ permeability allows paracellular penetration of toxic luminal substances, aggravating intestinal inflammation and mucosal injury. 3,22,23) Consumption of Cap in these clinical conditions may enhance increase in TJ permeability, resulting in greater mucosal penetration of luminal substances and further worsening of intestinal inflammation.…”

Intestinal permeability in strongyloidiasis

“…Impaired barrier function intensifies antigen access, which in turn leads to an exaggerated immune stimulation that initiates or perpetuates inflammation (2). Increased intestinal permeability has been described in inflammatory bowel disease (3)(4)(5)(6)(7)(8)(9)(10)(11), atopic eczema (12), celiac disease and dermatitis herpetiformis (13), cystic fibrosis (14,15), alcohol consumption (16), use of nonsteroidal antiinflammatory drugs (17)(18)(19)(20), and acute infectious diarrhea (12,21). On the other hand, decreased intestinal permeability has been demonstrated in Blastocystis hominis infection (22).…”