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01 April 2011

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

Krzysztof CelinskiABCDEF, Tomasz DworzanskiABCDEF, Agnieszka KorolczukABDF, Maria SlomkaBF, Sebastian RadejBDF, Halina Cichoz-LachBCDF, Agnieszka MadroBCDF

DOI: 10.12659/MSM.881712

Med Sci Monit 2011; 17(4): BR116-124


Background: This study sought to define the mechanism by which PPAR-gamma ligands affect the course of experimentally induced colitis in rats.
Material/Methods: Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARgamma 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.
Results: 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-gamma 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.
Conclusions: 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-gamma are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-gamma may contribute to development or relapse of nonspecific inflammatory bowel diseases.

Keywords: Peroxidase - blood, PPAR gamma - metabolism, Organ Size, Interleukin-6 - blood, Interleukin-10 - blood, Colon - pathology, Colitis - pathology, Body Weight, Rats, Wistar, Tissue Extracts

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750