Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs
(2018) In Gastroenterology 154(3). p.500-514- Abstract
Nonsteroidal 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 cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the 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 inhibition of COX enzymes, along with luminal... (More)
Nonsteroidal 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 cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the 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 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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- author
- Bjarnason, Ingvar ; Scarpignato, Carmelo ; Holmgren, Erik LU ; Olszewski, Michael ; Rainsford, Kim D and Lanas, Angel
- publishing date
- 2018-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Cyclooxygenase 1/metabolism, Cyclooxygenase 2/metabolism, Cyclooxygenase 2 Inhibitors/adverse effects, Cyclooxygenase Inhibitors/adverse effects, Gastrointestinal Diseases/chemically induced, Gastrointestinal Microbiome, Gastrointestinal Tract/drug effects, Helicobacter pylori/pathogenicity, Humans, Mitochondria/drug effects, Oxidative Phosphorylation/drug effects, Phospholipids/metabolism, Prostaglandins/metabolism
- in
- Gastroenterology
- volume
- 154
- issue
- 3
- pages
- 15 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85044317033
- pmid:29221664
- ISSN
- 1528-0012
- DOI
- 10.1053/j.gastro.2017.10.049
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
- id
- 35268c91-d7c2-44ea-83bd-fa19ac041693
- date added to LUP
- 2025-01-30 09:54:06
- date last changed
- 2025-07-05 03:33:33
@article{35268c91-d7c2-44ea-83bd-fa19ac041693,
abstract = {{<p>Nonsteroidal 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 cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the 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 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.</p>}},
author = {{Bjarnason, Ingvar and Scarpignato, Carmelo and Holmgren, Erik and Olszewski, Michael and Rainsford, Kim D and Lanas, Angel}},
issn = {{1528-0012}},
keywords = {{Animals; Cyclooxygenase 1/metabolism; Cyclooxygenase 2/metabolism; Cyclooxygenase 2 Inhibitors/adverse effects; Cyclooxygenase Inhibitors/adverse effects; Gastrointestinal Diseases/chemically induced; Gastrointestinal Microbiome; Gastrointestinal Tract/drug effects; Helicobacter pylori/pathogenicity; Humans; Mitochondria/drug effects; Oxidative Phosphorylation/drug effects; Phospholipids/metabolism; Prostaglandins/metabolism}},
language = {{eng}},
number = {{3}},
pages = {{500--514}},
publisher = {{Elsevier}},
series = {{Gastroenterology}},
title = {{Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs}},
url = {{http://dx.doi.org/10.1053/j.gastro.2017.10.049}},
doi = {{10.1053/j.gastro.2017.10.049}},
volume = {{154}},
year = {{2018}},
}