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

Abstract

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.

Glucagon-Like Peptide-2 and Common Therapeutics in a Murine Model of Ulcerative Colitis

“…Treatment of DSS-mice with ASA enhanced survival slightly, consistent with the results of a previous study (Axelsson et al, 1998). However, more importantly, ASA administration did not diminish the beneficial effects of GLP-2 on either survival or CDS.…”

“…Colitis was induced by the placement of DSS (molecular weight 40,000 -50,000; Amersham Biosciences Inc., Baie d'Urfé, QC, Canada) in the drinking water for 10 consecutive days (Axelsson et al, 1998;Drucker et al, 1999;Egger et al, 1999). After titration of DSS in preliminary studies, a concentration of 3.5% DSS (w/v) was chosen to get a balance between severity and survival.…”

Dextran Sodium Sulfate-Induced Colitis in Germ-Free IQI/Jic Mice.

“…Both acute and chronic colitis can be induced by changing the concentration of DSS or by the administration of multiple doses of DSS [21]. DSSinduced colitis is considered to be a good model for human UC and it has been used to evaluate the effects of anti-inflammatory drugs [1,2,18,19]. Despite its widespread use as a model, the pathogenesis of DSSinduced colitis is still unclear.…”

The 13C-Butyrate Breath Test: a New Non-Invasive Method for Assessing Colitis in a Murine Model

“…Therefore, it is necessary to investigate butyrate metabolism not only in humans but also in experimental murine colitis. Efficacy of salicylazosulfapyridine (SASP) in DSS murine colitis has been reported (12,13). So we studied whether the measurement of expired 13 CO 2 after rectal administration of 13 C-butyrate by the breath test can be used to assess the phase of inflammation and amelioration of inflammation after treatment with SASP in DSS murine colitis.…”