Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs

Bjarnason, I. ; Scarpignato, C. ; Holmgren, E. ; Olszewski, M. ; Rainsford, K.D. ; Lanas, A. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1053/j.gastro.2017.10.049

Año: 2018

Publicado en: Gastroenterology 154, 3 (2018), 500-514
ISSN: 0016-5085

Factor impacto JCR: 19.233 (2018)

Categ. JCR: GASTROENTEROLOGY & HEPATOLOGY rank: 2 / 84 = 0.024 (2018) - Q1 - T1

Factor impacto SCIMAGO: 7.384 - Hepatology (Q1) - Gastroenterology (Q1)

Tipo y forma: Revisión (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)