Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs
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 involve...
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| Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2018-02, Vol.154 (3), p.500-514 |
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| container_title | Gastroenterology (New York, N.Y. 1943) |
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| creator | Bjarnason, Ingvar Scarpignato, Carmelo Holmgren, Erik Olszewski, Michael Rainsford, Kim D. Lanas, Angel |
| description | 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. |
| doi_str_mv | 10.1053/j.gastro.2017.10.049 |
| format | Article |
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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. 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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. 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| source | MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection |
| subjects | Animals Bacteria Bile Acids Cyclooxygenase 1 - metabolism Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - adverse effects Cyclooxygenase Inhibitors - adverse effects Drug-Induced Intestinal Damage Gastrointestinal Diseases - chemically induced Gastrointestinal Diseases - diagnosis Gastrointestinal Diseases - metabolism Gastrointestinal Diseases - microbiology Gastrointestinal Microbiome Gastrointestinal Tract - drug effects Gastrointestinal Tract - metabolism Gastrointestinal Tract - microbiology Gastrointestinal Tract - pathology Helicobacter pylori - pathogenicity Humans Mitochondria - drug effects Mitochondria - metabolism Oxidative Phosphorylation - drug effects Phospholipids - metabolism Prostaglandin Prostaglandins - metabolism |
| title | Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs |
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