Small Intestinal Injury Caused by NSAIDs/Aspirin: Finding New from Old

Abstract

Small intestinal injury caused by non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin is an epoch making topic in clinical field with the aid of new devices, capsule endoscopy and double balloon enteroscopy to look at small intestine directly. However, the injury has been reported in animals since more than 40 years ago. Proposed mechanisms are impairment of mucosal defense through inhibition of cyclooxygenase (COX) resulting in deficiency of prostaglandins, and mitochondrial disorder. Possible aggressive factors are NSAIDs/aspirin themselves, bile, and enterobacteria. Translocation of enterobacteria through the mucosa impaired integrity may be the first step of the injury. Bacterial lipopolysaccharides stimulate toll-like receptor-4 in macrophages, which increases proinflammatory cytokines through MyD88 signaling pathway. Finally neutrophils are activated and the small intestinal mucosa is injured with the attacks of NSAIDs/aspirin themselves, bile, and proteolytic enzymes and active oxygen species released by neutrophils. Candidates of treatment tools are prostaglandin derivatives, mucoprotective drugs, probiotics, and mitochondrial protective drugs such as metronidazole and cyclosporin A. Further clinical studies are needed to elucidate the effect in humans.

MDR1 is Related to Intestinal Epithelial Injury Induced by Acetylsalicylic Acid

“…Oral administration of aspirin does not cause small intestinal epithelial cellular injury directly because aspirin is rapidly absorbed from the stomach and duodenum under acidic conditions and because of the lack of enterohepatic recirculation [7]. However, recent enteroscopic studies have clearly demonstrated that low-dose aspirin (usually enteric-coated) induces hemorrhagic lesions, including ulcers and bleeding, in the small intestine in patients.…”

Clinical importance of nonsteroidal anti-inflammatory drug enteropathy: the relevance of tumor necrosis factor as a promising target

“…TNF has been reported to up-regulate the expression of nucleotide-binding oligomerization domain 2 (NOD2) gene in intestinal epithelial cells leading to subsequent increase in their lipopolysaccharide (LPS) susceptibility [75]. LPS, which is a highly pathogenic component of the walls of gram-negative bacteria has been reported to mediate the release of TNF from macrophages via MyD88 through Toll like receptor (TLR)-4 [134,137]. Similar rise in the level of TNF was observed in the small intestine of mice given indomethacin [134,138,139].…”

“…While, targeting enteric bacteria with a poorly absorbed antibiotic (like rifaximin), covering gram-positive and gram-negative bacteria (both aerobic and anaerobic) has been reported to attenuate the myeloperoxidase (MPO) and TNF tissue levels [140]. However, if left untreated, this consistent rise in TNF also activates neutrophils, which once entered the bowel microcirculation, undergo a rapid activation leading to tissue invasion, with massive production of injurious substances such as proteolytic enzymes and detrimental ROS leading to exacerbation of small intestinal injury [137]. [134,137].…”

Antiplatelet therapy with acetylsalicylic acid: Approaches to reducing the frequency of gastrointenstinal adverse reactions

“…По-вреждение клеточных мембран и расширение межклеточных пространств эпителия увеличивают проницаемость последнего для желчных кислот и протеолитических ферментов. Следствием нарушения барьерной функции СО кишки также становится транслокация энтеробактерий с дальнейшей интенсификацией воспалительного процесса [18].…”