EXPERIMENTAL COLITIS INDUCED BY DEXTRAN SULFATE SODIUM IN MICE - BENEFICIAL-EFFECTS OF SULFASALAZINE AND OLSALAZINE

Background: Animal models of inflammatory bowel disease are artificial and more or less representative of human disease. However, the dextra n sulphate sodium (DSS) induced intestinal inflammation model has rece ntly been shown to fulfil some pathological criteria for an adequate e xperimental model. Aim: To determine whether this form of experimental intestinal inflammation responds to established therapy used for huma n inflammatory bowel disease. Methods: DSS was used to induce intestin al inflammation in conventional Balb/c mice and athymic nu/nu CD-1 (BR ) mice, and the well-documented 5-aminosalicylic acid (5-ASA) based an ticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used t o study therapeutic effects. Parameters which have been shown to refle ct DSS-induced intestinal inflammation (body weight, colon length, spl een weight, diarrhoea, and rectal bleeding) were measured in the Balb/ c mice. Results: Significant amelioration was seen on these parameters after different treatment protocols. Survival in nu/nu CD-1 mice was studied, and after 16 days a death rate of 50% was noted in the DSS gr oup. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day) significantly prolong ed the survival to 29 and 38 days, respectively. SASP and OLZ showed a dose-dependent effect in the range between 10 and 100 mg/kg/day, dose s closely corresponding to those used in humans. Conclusions: SASP and OLZ are able to ameliorate the DSS-induced intestinal inflammation, T he dose-response patterns suggested that the active therapeutic moiety for the two drugs appears to be mainly the liberated 5-ASA molecule.