Mechanisms of damage to the gastrointestinal tract from non-steroidal anti-inflammatory drugs

BJARNASON, Ingvar, SCARPIGNATO, Carmelo, HOLMGREN, Erik, OLSZEWSKI, Michael, RAINSFORD, Kim and LANAS, Angel (2017). Mechanisms of damage to the gastrointestinal tract from non-steroidal anti-inflammatory drugs. Gastroenterology, 154 (3), 500-514.

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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. [Abstract copyright: Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.]

Item Type:	Article
Additional Information:	** From PubMed via Jisc Publications Router. ** History: received 14-03-2017; revised 28-10-2017; accepted 31-10-2017.
Uncontrolled Keywords:	GI, bacteria, bile acids, drug-induced intestinal damage, prostaglandin
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1053/j.gastro.2017.10.049
Page Range:	500-514
SWORD Depositor:	Margaret Boot
Depositing User:	Margaret Boot
Date Deposited:	03 Jan 2018 16:39
Last Modified:	18 Mar 2021 01:23
URI:	https://shura.shu.ac.uk/id/eprint/17716

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