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

Abstract

BACKGROUND:

This study sought to define the mechanism by which PPAR-γ 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 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.

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-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.

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-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.

• Authors: Krzysztof Celinski, Tomasz Dworzanski, Agnieszka Korolczuk, Maria Slomka, Sebastian Radej, Halina Cichoz-Lach, Agnieszka Madro
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 17 Issue 4 Pg. BR116-24 (Apr 2011) ISSN: 1643-3750 [Electronic] United States
• PMID: 21455100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• PPAR gamma
• Tissue Extracts
• Interleukin-10
• Peroxidase

Topics

• Animals
• Body Weight
• Colitis (blood, chemically induced, metabolism, pathology)
• Colon (metabolism, pathology)
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Organ Size
• PPAR gamma (metabolism)
• Peroxidase (blood)
• Rats
• Rats, Wistar
• Tissue Extracts