Fiche publication
Date publication
mars 2026
Journal
Basic & clinical pharmacology & toxicology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VILLA Pascal
Tous les auteurs :
Brossier C, Sauvage FL, Valencia-Schmitt C, Calco V, Villa P, Marquet P, Lawson R
Lien Pubmed
Résumé
Mycophenolic acid (MPA) is a widely used immunosuppressant whose use is often limited by gastrointestinal toxicity. Gut bacterial hydrolysis of liver-derived MPA glucuronides increases local exposure to MPA, potentially impairing epithelial barrier function and cellular metabolism. To explore the effects of MPA on gut barrier integrity and metabolic pathways in gut epithelial cells, Caco-2 cells were exposed to MPA (10 or 100 μM), and barrier function was assessed by transepithelial electrical resistance (TEER) and lucifer yellow (LY) permeability in both differentiated and early-stage monolayers, while intracellular metabolic changes were investigated using targeted LC-MS/MS metabolomics. In differentiated monolayers, MPA did not significantly alter LY transport or TEER measurements. In contrast, MPA exposure during the early stages of monolayer formation reduced TEER values, 3 days after MPA withdrawal (Day 6; p < 0.01). The effects of 100-μM MPA were still noticeable at Day 10, as confirmed by LY permeability (p < 0.05). Metabolomic profiling clearly separated exposed from control cells (PCA, PC1 + PC2 = 92% variance). At 10 and 100 μM, 9 and 8 metabolites were significantly altered, with 6 common to both doses. Pathway enrichment revealed perturbations mainly in nucleotide synthesis, consistent with altered metabolic activity.
Mots clés
Caco‐2 cells, MPA‐induced enteropathy, gut epithelial barrier, lucifer yellow, mycophenolic acid (MPA), targeted metabolomics, transepithelial electrical resistance
Référence
Basic Clin Pharmacol Toxicol. 2026 03;138(3):e70204
