NSAID-Associated Small Intestinal Injury: An Overview From Animal Model Development to Pathogenesis, Treatment, and Prevention

Abstract

With the wide application of non-steroidal anti-inflammatory drugs (NSAIDs), their gastrointestinal side effects are an urgent health burden. There are currently sound preventive measures for upper gastrointestinal injury, however, there is a lack of effective defense against lower gastrointestinal damage. According to a large number of previous animal experiments, a variety of NSAIDs have been demonstrated to induce small intestinal mucosal injury in vivo. This article reviews the descriptive data on the administration dose, administration method, mucosal injury site, and morphological characteristics of inflammatory sites of various NSAIDs. The cells, cytokines, receptors and ligands, pathways, enzyme inhibition, bacteria, enterohepatic circulation, oxidative stress, and other potential pathogenic factors involved in NSAID-associated enteropathy are also reviewed. We point out the limitations of drug modeling at this stage and are also pleased to discover the application prospects of chemically modified NSAIDs, dietary therapy, and many natural products against intestinal mucosal injury.

Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Gastroprotective NSAIDs on the Gastrointestinal Tract: A Narrative Review

“…[51][52][53]. The use of gastroprotective slow-release preparations shifted the disease burden to lower GIT and has set the way for several researchers to find the side effects of NSAIDs in the small and large intestines [54].…”

“…Dyspepsia (chronic indigestion that presents as stomach fullness, bloating, and upper abdominal pain during or immediately following food intake) is not only the most common side effect of NSAIDs but also the leading cause of premature discontinuation of the drug [49,52,56]. Although there are several other causes of dyspepsia besides NSAIDs, it is crucial to determine the association of dyspepsia with NSAID use as 10% of patients stop using NSAIDs because of associated dyspepsia [51,54]. Its diagnosis is made clinically, and no structural lesion is found on endoscopy [57].…”

“…While slow-release formulations reduce the upper GIT side effects, the lower GIT side effects still pose a concern. To mitigate these side effects, strategies such as using COX-2 selective NSAIDs, NO-releasing NSAIDs, and dual COX/LOX inhibiting drugs have been employed, which have similar therapeutic efficacy to tNSAIDs but with a lower risk of GIT side effect [ 54 ].…”

Nonacidic thiophene‐based derivatives as potential analgesic and design, synthesis, biological evaluation, and metabolic stability study

“…However, in the past, researchers had focused on controlling gastric complications. Nowadays, especially after the development of NSAID enteric‐coated preparations, NSAID‐associated enteropathy has received more attention (Scarpignato & Hunt, 2010; Zhang et al, 2022).…”

Pharmacological Assessment of Constituents of Species Allium Saxatile and Allium Ponticum Growing in Georgia

“…* -p<0.01 vs control group.ConclusionComparative study of A. ponticum and A. saxatile pharmacological efficacy revealed the advantage of the latter, and the same tendency was noticed when separate fractions were studied. In particular, total extract of A. saxatile is characterized with marked analgesic and anti-inflammatory activity presumably because of A.S-F3 content, that well correlates with the worsening of gastric mucosa condition, suggesting having mechanism of action similar to the one of NSAIDs[29]. At the same time pronounced analgesic activity of A. ponticum should be taken into consideration, as well, but its mechanism of action remains unclear and thus needs further justification.…”