Comparison of the anti-inflammatory and therapeutic actions of PPAR-gamma agonists rosiglitazone and troglitazone in experimental colitis.
Krzysztof Celiński, T Dworzański, R Fornal, Agnieszka Korolczuk, Agnieszka Mądro, Maria Słomka
Abstract
Krzysztof Celiński, T Dworzański, R Fornal, Agnieszka Korolczuk, Agnieszka Mądro, Maria Słomka
Abstract
Non-specific inflammatory bowel diseases, including ulcerative colitis and Crohn`s disease, are chronic non-infectious diseases that showed an increase in prevalence in recent years, particularly in the developed countries. The effective methods of their treatment and prevention of recurrences are currently under investigation. One type of therapy that can prevent the inflammatory recurrence in the gastrointestinal tract is the PPAR-γ agonists thiazolidinediones. Numerous studies available in literature have confirmed the beneficial effects of thiazolidinediones (glitazones), namely rosiglitazone and troglitazone in the gut. The objective of the present study was to compare the possible effects of rosiglitazone 10 mg/kg b.w. or 30 mg/kg b.w. and troglitazone 30 mg/kg b.w. on experimental colitis induced by administration of 1.5% dextran sodium sulphate (DSS) administered in drinking water to rats. Specimens collected from the large intestine were microscopically evaluated, and concentrations of Th1- dependent (IL-2, INF) and Th2-dependent (IL-4, IL-10) cytokines were determined in the serum and intestinal homogenates. Both rosiglitazone and troglitazone have demonstrated significant anti-inflammatory properties. This observation was confirmed by histopathological and immunoenzymatic tests. The therapeutic efficacy of rosiglitazone was dose-dependent. Troglitazone resulted in significantly stronger enhancement of anti-inflammatory cytokine expression than rosiglitazone and comparable downregulation of pro-inflammatory cytokine expression compared to rosiglitazone used in a higher dose.
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Non-specific inflammatory bowel diseases, including ulcerative colitis and Crohn`s disease, are chronic non-infectious diseases that showed an increase in prevalence in recent years, particularly in the developed countries. The effective methods of their treatment and prevention of recurrences are currently under investigation. One type of therapy that can prevent the inflammatory recurrence in the gastrointestinal tract is the PPAR-γ agonists thiazolidinediones. Numerous studies available in literature have confirmed the beneficial effects of thiazolidinediones (glitazones), namely rosiglitazone and troglitazone in the gut. The objective of the present study was to compare the possible effects of rosiglitazone 10 mg/kg b.w. or 30 mg/kg b.w. and troglitazone 30 mg/kg b.w. on experimental colitis induced by administration of 1.5% dextran sodium sulphate (DSS) administered in drinking water to rats. Specimens collected from the large intestine were microscopically evaluated, and concentrations of Th1- dependent (IL-2, INF) and Th2-dependent (IL-4, IL-10) cytokines were determined in the serum and intestinal homogenates. Both rosiglitazone and troglitazone have demonstrated significant anti-inflammatory properties. This observation was confirmed by histopathological and immunoenzymatic tests. The therapeutic efficacy of rosiglitazone was dose-dependent. Troglitazone resulted in significantly stronger enhancement of anti-inflammatory cytokine expression than rosiglitazone and comparable downregulation of pro-inflammatory cytokine expression compared to rosiglitazone used in a higher dose.
Key concepts: Rosiglitazone, Troglitazone, Medicine, Pharmacology, Inflammatory bowel disease, Colitis, Ulcerative colitis, Internal medicine