BACKGROUND: Animal models of inflammatory bowel disease are artificial and more or less representative of human disease. However, the dextran sulphate sodium (DSS) induced intestinal inflammation model has recently been shown to fulfil some pathological criteria for an adequate experimental model. AIM: To determine whether this form of experimental intestinal inflammation responds to established therapy used for human inflammatory bowel disease. METHODS: DSS was used to induce intestinal inflammation in conventional Balb/c mice and athymic nu/nu CD-1(BR) mice, and the well-documented 5-aminosalicylic acid (5-ASA) based anticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used to study therapeutic effects. Parameters which have been shown to reflect DSS-induced intestinal inflammation (body weight, colon length, spleen 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 group. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day) significantly prolonged 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, doses closely corresponding to those used in humans. CONCLUSIONS: SASP and OLZ are able to ameliorate the DSS-induced intestinal inflammation. The dose-response patterns suggested that the active therapeutic moiety for the two drugs appears to be mainly the liberated 5-ASA molecule.
BACKGROUND: Animal models of inflammatory bowel disease are artificial and more or less representative of human disease. However, the dextran sulphate sodium (DSS) induced intestinal inflammation model has recently been shown to fulfil some pathological criteria for an adequate experimental model. AIM: To determine whether this form of experimental intestinal inflammation responds to established therapy used for humaninflammatory bowel disease. METHODS:DSS was used to induce intestinal inflammation in conventional Balb/c mice and athymic nu/nu CD-1(BR)mice, and the well-documented 5-aminosalicylic acid (5-ASA) based anticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used to study therapeutic effects. Parameters which have been shown to reflect DSS-induced intestinal inflammation (body weight, colon length, spleen 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-1mice was studied, and after 16 days a death rate of 50% was noted in the DSS group. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day) significantly prolonged 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, doses closely corresponding to those used in humans. CONCLUSIONS:SASP and OLZ are able to ameliorate the DSS-induced intestinal inflammation. The dose-response patterns suggested that the active therapeutic moiety for the two drugs appears to be mainly the liberated 5-ASA molecule.
Authors: O Morteau; S G Morham; R Sellon; L A Dieleman; R Langenbach; O Smithies; R B Sartor Journal: J Clin Invest Date: 2000-02 Impact factor: 14.808
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