NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND INFLAMMATORY BOWEL DISEASE: CURRENT PERSPECTIVES
Section snippets
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed drugs because of their anti-inflammatory and analgesic properties. However, their use is associated with an elevated risk of damage to the gastrointestinal mucosa and related complications 1., 2., 3., 4.. Henry et al. [5] studied the relative risk of gastrointestinal complications using a meta-analytical approach: the meta-analysis showed wide differences among individual drugs, although some of the differences may be
MECHANISMS LEADING TO INTESTINAL DAMAGE
An enteropathy can be detected in 20–60% of NSAIDs recipients, depending on the method used for the diagnosis 14., 15.. Although most of the clinical evidence on the intestinal adverse effects of NSAIDs comes from case reports [16], several experimental studies in animals allowed to put forward different hypotheses to explain the possible mechanisms of enteric toxicity.
COX INHIBITORS AND IBD
Animal models of IBD support the contention that eicosanoids are involved in modulating tissue inflammation [47], but the studies on the impact of COX-2 inhibition on animal models of colitis are widely dissonant (Table II). In accordance with the central role of eicosanoids in maintaining the inflammatory process, Karmeli et al. [48] demonstrated that COX-2 inhibitors have a beneficial effect on experimental colitis in rats, acting by reducing colonic eicosanoids generation. In contrast,
CURRENT PERSPECTIVES
An aspect that is often overlooked is that every NSAID (whether or not it is a selective COX-2 inhibitor) is endowed with a range of pharmacological activities that may lead to significant differences in the effects of an individual agent on the inflamed mucosa. For instance, the salicylic acid derivative 5-ASA is widely used in the treatment of IBD, and its anti-inflammatory action is due to inhibition of activation of transcription factor NF-κB [13].
NF-κB designates a group of transcription
CONCLUSIONS
From the preceding paragraphs, it emerges that the mechanisms leading to intestinal damage by NSAIDs are different from those underlying the gastric damage. Moreover, the two different isoforms of COX seem to play different roles in maintaining homeostasis of gastrointestinal mucosa and in the process of gastrointestinal ulcer healing.
The impact of COX-2 selective inhibitors on IBD is currently controversial: on one hand, COX inhibition is fundamental for the modulation of the inflammatory
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