Comparison of anti-inflammatory properties of peroxisome proliferator-activated receptor gamma agonists rosiglitazone and troglitazone in prophylactic treatment of experimental colitis.

Non-specific inflammatory bowel disease (IBD), including ulcerative colitis and Crohn`s disease, is a chronic noninfectious inflammatory disease whose incidence is increasingly high, especially in the developed countries. Effective methods of its treatment and prevention of recurrences are still under investigation. Amongst the options to control effectively the inflammatory processes of the gastrointestinal tract are thiazolidinediones - peroxisome proliferator-activated receptors gamma (PPAR-γ) agonists, whose beneficial effects on macroscopic and histopathological features of colitis have been confirmed in numerous studies. In the present study, possible effects of PPAR-γ agonists rosiglitazone and troglitazone enhancing the resistance of colonic tissues to the damaging factor were examined and compared. Rats received the food with 0.01% rosiglitazone or troglitazone for 4 weeks; during the final 2 weeks, colitis-inducing 1.5% DSS (dextran sodium sulfate) was additionally administered in the drinking water. The large intestine specimens were microscopically evaluated and the levels of Th1- (IL-2, INF) and Th2-dependent (IL-4, IL-10) cytokines were determined in the serum and intestinal homogenates. Prophylactic treatment with rosiglitazone and troglitazone ameliorated colitis substantially down-regulating the microscopic inflammatory parameters. Rosiglitazone and troglitazone administered before the induction of colitis exerted comparable effects on colitis. Both substances significantly reduced the levels of pro-inflammatory cytokines and increased the levels of inflammation-limiting cytokines. We conclude that thiazolidinedione drugs are likely to be successfully used for therapy and prevention of non-specific bowel diseases.