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Mechanisms of Damage to the Gastrointestinal Tract From Non-steroidal Anti-inflammatory Drugs

Research output: Contribution to journalArticle

Ingvar Bjarnason ; Carmelo Scarpignato ; Erik Holmgren ; Michael Olszewski ; Kim D. Rainsford ; Angel Lanas

Original languageEnglish
JournalGastroenterology
Early online date6 Dec 2017
DOIs
StateE-pub ahead of print - 6 Dec 2017

King's Authors

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal tract, causing widespread morbidity and mortality. Although mechanisms of damage involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or COX1) and PTGS1 (COX2), other factors are involved. We review mechanisms of gastrointestinal damage induction by NSAIDs, via COX-mediated and COX-independent processes. NSAIDs interact with phospholipids and uncouple mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the gastrointestinal barrier. The resulting increase in intestinal permeability leads to low-grade inflammation. NSAID’s inhibition of COX enzymes, along with luminal aggressors, results in erosions and ulcers, with potential complications of bleeding, protein loss, stricture formation, and perforation. We propose a model for NSAID-induced damage to the gastrointestinal tract that includes these complex, interacting, and inter-dependent factors. This model highlights the obstacles for the development of safer NSAIDs.

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