Differential Effects of Nonsteroidal Anti-Inflammatory Drugs in an In Vitro Model of Human Leaky Gut

被引：6

作者：

d'Angelo, Michele ^{[1
]}

Brandolini, Laura ^{[2
]}

Catanesi, Mariano ^{[1
]}

Castelli, Vanessa ^{[1
]}

Giorgio, Cristina ^{[3
]}

Alfonsetti, Margherita ^{[1
]}

Tomassetti, Mara ^{[3
]}

Zippoli, Mara ^{[3
]}

Benedetti, Elisabetta ^{[1
]}

Cesta, Maria Candida ^{[2
]}

Colagioia, Sandro ^{[2
]}

Cocchiaro, Pasquale ^{[3
]}

Cimini, Annamaria ^{[1
,4
]}

Allegretti, Marcello ^{[2
]}

机构：

[1] Univ Aquila, Dept Life Hlth & Environm Sci, I-67100 Laquila, Italy

[2] Dompe Farmaceut SpA, Via Campo Pile Snc, I-67100 Laquila, Italy

[3] Dompe Farmaceut SpA, Via Amicis 95, I-80131 Naples, Italy

[4] Temple Univ, Sbarro Inst Canc Res & Mol Med, Dept Biol, Philadelphia, PA 19122 USA

来源：

CELLS | 2023年 / 12卷 / 05期

关键词：

inflammation; oxidative stress; anti-inflammatory; macrophages; transepithelial electrical resistance; tight junction; NF-KAPPA-B; ACUTE ALCOHOL-INTOXICATION; INTESTINAL BARRIER; PPAR-GAMMA; KETOPROFEN; INHIBITION; ACTIVATION; EXPRESSION; LYSINE; CYCLOOXYGENASE-2;

D O I：

10.3390/cells12050728

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：22