Ponferrada Díaz, ÁngelCaso Fernández, Javier RubénAlou Cervera, LuisColón Rodríguez, Arturo LuisSevillano Fernández, DavidMoro Sánchez, María ÁngelesLizasoaín Hernández, IgnacioGómez-Lus Centelles, María LuisaLorenzo Fernández, PedroCos Arregui, EnriqueLeza Cerro, Juan CarlosMenchén Viso, Luis Alberto2024-07-242024-07-242007-05Ponferrada A, Caso JR, Alou L, Colón A, Sevillano D, Moro MA, Lizasoain I, Menchén P, Gómez-Lus ML, Lorenzo P, Cos E, Leza JC, Menchén L. The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction. Gastroenterology. 2007 May;132(5):1791-803.0016-508510.1053/j.gastro.2007.02.032https://hdl.handle.net/20.500.14352/107097Background & aims: Psychological stress has been implicated in the clinical course of several gastrointestinal diseases, but the mechanisms implicated and the effects of stress on the normal colon are not yet fully understood. Methods: Male Wistar rats were exposed to various immobilization periods as a stress paradigm. Colon was processed to assess myeloperoxidase activity, nitric oxide synthase 2, cyclooxygenase 2, and peroxisome proliferator-activated receptor gamma (PPARgamma) expression and production of prostaglandins. Colonic permeability, bacterial translocation, tight junctions ultrastructure, and immunoglobulin (Ig) A levels were also evaluated. Results: Exposure to acute (6 hours) immobilization stress produced an increase in myeloperoxidase activity and nitric oxide synthase 2 and cyclooxygenase 2 expression. All these parameters remained increased after 5 days of repeated stress exposure, showing a trend to normalize after 10 days. Levels of the anti-inflammatory eicosanoid 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and expression of PPARgamma run parallel with these changes. Colonic epithelial barrier was altered after stress exposure, and a significant decrease in colonic IgA levels after acute stress exposure was observed. Pretreatment with PPARgamma agonists 15d-PGJ(2) and rosiglitazone prevented colonic inflammation and barrier dysfunction as well as the decrease of IgA production induced after acute stress; PPARgamma specific antagonist T0070907 reverted these effects. Conclusions: Activation of PPARgamma in rat colon in vivo seems to counteract colonic inflammation and dysfunction induced by stress. On the other hand, PPARgamma ligands may be therapeutically useful in conditions in which inflammation and barrier dysfunction takes place in colon after exposure to stress.engjournal articlehttps://doi.org/10.1053/j.gastro.2007.02.032https://www.sciencedirect.com/science/article/pii/S0016508507003897restricted access611.02615Farmacología (Medicina)Microbiología médicaGastroenterología y hepatología2414 Microbiología3209 Farmacología3205.03 Gastroenterología