Activated and inactivated PPARs-γ modulate experimentally induced colitis in rats

• Published in: Medical science monitor Vol. 17; no. 4; pp. BR116 - BR124
• Main Authors: Celinski, Krzysztof, Dworzanski, Tomasz, Korolczuk, Agnieszka, Slomka, Maria, Radej, Sebastian, Cichoz-Lach, Halina, Madro, Agnieszka
• Format: Journal Article
• Language: English
• Published: United States International Scientific Literature, Inc 01.04.2011
• Subjects: Animals; Basic Research; Body Weight; Colitis - blood; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Colon - metabolism; Colon - pathology; Interleukin-10 - blood; Interleukin-6 - blood; Organ Size; Peroxidase - blood; PPAR gamma - metabolism; Rats; Rats, Wistar; Tissue Extracts
• ISSN: 1234-1010; 1643-3750
• DOI: 10.12659/MSM.881712

This study sought to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats. Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), was administrated intraperitoneally 120 mg/kg 4 times every other day. Rosiglitazone 8 mg/kg was administrated by gastric tube 4 times. Body weight was measured daily. After killing, the large intestinal tissue was weighed and collected for histopathologic and immunoenzymatic tests. Levels of IL-6, IL-10, and myeloperoxidase (MPO) were determined in serum and in intestinal homogenates. Rats receiving rosiglitazone had higher body weight, whereas large intestine weight/length ratio was lower; histology showed fewer inflammatory markers. Rats receiving TNBS and TNBS along with BADGE had more intensive inflammatory changes. Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10. Decreased levels of MPO indicate reduced neutrophil-dependent immune response. The antagonist of PPAR-γ increased IL-6 in serum and decreased IL-10 in intestinal homogenates. Bisphenol A diglycidyl ether administrated to healthy animals increases serum IL-6 levels. Rosiglitazone inhibits experimental inflammation; administration of its selective antagonist abolishes this protective influence. Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10. Agonists of PPARs-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.