Differential Effects of Nonsteroidal Anti-Inflammatory Drugs in an In Vitro Model of Human Leaky Gut.
Cells
; 12(5)2023 02 24.
Article
de En
| MEDLINE
| ID: mdl-36899865
ABSTRACT
The intestinal barrier is the main contributor to gut homeostasis. Perturbations of the intestinal epithelium or supporting factors can lead to the development of intestinal hyperpermeability, termed "leaky gut". A leaky gut is characterized by loss of epithelial integrity and reduced function of the gut barrier, and is associated with prolonged use of Non-Steroidal Anti-Inflammatories. The harmful effect of NSAIDs on intestinal and gastric epithelial integrity is considered an adverse effect that is common to all drugs belonging to this class, and it is strictly dependent on NSAID properties to inhibit cyclo-oxygenase enzymes. However, different factors may affect the specific tolerability profile of different members of the same class. The present study aims to compare the effects of distinct classes of NSAIDs, such as ketoprofen (K), Ibuprofen (IBU), and their corresponding lysine (Lys) and, only for ibuprofen, arginine (Arg) salts, using an in vitro model of leaky gut. The results obtained showed inflammatory-induced oxidative stress responses, and related overloads of the ubiquitin-proteasome system (UPS) accompanied by protein oxidation and morphological changes to the intestinal barrier, many of these effects being counteracted by ketoprofen and ketoprofen lysin salt. In addition, this study reports for the first time a specific effect of R-Ketoprofen on the NFkB pathway that sheds new light on previously reported COX-independent effects, and that may account for the observed unexpected protective effect of K on stress-induced damage on the IEB.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Kétoprofène
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Cells
Année:
2023
Type de document:
Article
Pays d'affiliation:
Italie