Actions of sulphasalazine and analogues in animal models of experimental colitis

Axelsson, Lars-Göran; Ahlstedt, S.

doi:10.1007/bf02660614

Cited by 11 publications

(9 citation statements)

References 106 publications

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“…How the in¯ammation is induced in different animal models, and how the animals respond to treatment, should also enable a further elucidation of intestinal in¯ammation pathogenesis and the actions of the relevant drugs. 10 We have shown in this study that DSS-induced intestinal in¯ammation can be palliated by treatment with SASP or OLZ. These effects were seen in conventional Balb/c mice as a reduced severity of some of the pathological effects of DSS, i.e.…”

Section: Discussionmentioning

confidence: 55%

“…Parameters which have been shown to discuss animal models in terms of the features of the human disease which they are intended to resemble. 10 DSS-induced colitis exhibits 1,8,9 some of the clinical and histological in¯ammatory features which are found in humans with ulcerative colitis. 11±14 Thus, DSSinduced in¯ammation of the colon originates in the distal colon, progressing to involve the whole colon and in severe cases the caecum.…”

Section: Introductionmentioning

confidence: 99%

“…1,2,8,15,16,18 To further strengthen the relevance of the DSS model, the induced in¯ammation should respond to treatment with drugs which have been generally accepted and used for the treatment of in¯ammatory bowel disease in humans. 10 DSS-induced in¯ammation has been shown to be mitigated by treatment with experimental therapeutic principles, for example, the antioxidant compound MDL73404, the immuno-suppressant FK506. 17,19 DSS-induced in¯ammation also responds favourably to treatment with cyclosporin, an immunosuppressant drug which is used to treat in¯ammatory bowel disease in humans.…”

Section: Introductionmentioning

confidence: 99%

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

Axelsson¹,

Landström²,

Bylund-Fellenius³

1998

Aliment Pharmacol Ther

106

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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.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Axelsson¹,

Landström²,

Bylund-Fellenius³

1998

Aliment Pharmacol Ther

106

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“…DSS is a synthetized sulfated polyglucan, and thus is a purer substance and produces a more reproducible response than the natural polygalactan z-carrageenan, which has been used previously to induce inflammation in the gut [5].…”

Section: Introductionmentioning

confidence: 99%

“…To study autoimmune mechanisms in the gut, and the effect of immunomodulating drugs, relevant animal models of intestinal inflammation are imperative [5]. One such model is the dextran sulfate sodium (DSS) induced colitis model.…”

Section: Introductionmentioning

confidence: 99%

Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4+-cell depleted, athymic and NK-cell depleted SCID mice

Landström²,

et al. 1996

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Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.

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Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis

Renes

Boshuizen

Nispen

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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Actions of sulphasalazine and analogues in animal models of experimental colitis

Cited by 11 publications

References 106 publications

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

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

Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4+-cell depleted, athymic and NK-cell depleted SCID mice

Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis

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