Experimental colitis induced by dextran sulphate sodium in mice: beneficial effects of sulphasalazine and olsalazine.
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.


OBJECTIVE
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.
Pharmacia & Upjohn, Department of Pharmacology, Uppsala, Sweden. lars-goran.axelsson@eu.pnu.com
L G
LG
Axelsson
E
E
Landström
A C
AC
Bylund-Fellenius
D000636:Aminosalicylic Acids / Q000627:therapeutic use*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017063:Outcome Assessment, Health Care; D012460:Sulfasalazine / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000636:Aminosalicylic Acids; D005765:Gastrointestinal Agents; D012460:Sulfasalazine; D016264:Dextran Sulfate; C032587:olsalazine