Dextran Sulfate Salt Induced Colitis (DSS) in Rat

Induction:

Rats are exposed to Dextran Sulfate Salt (DSS) in water for 5 to 7 days to induce inflammation and gland loss with erosion in the colon.

Disease Parameters:

Rats have been shown to develop acute colitis with signs of diarrhea, gross rectal bleeding, and body weight loss within 6 to 10 days after ingesting DSS. Gross and histopathologic changes resulting from this treatment resemble somewhat those occurring in human ulcerative colitis, a subset of inflammatory bowel disease.1–5

Dosing Paradigms:

  • Dosing is initiated prior to or once exposure to DSS begins and continues until study termination.
  • Route of administration: SC, PO, IP, IV, IC

Clinical Assessment:

Rats are weighed and water consumption is measured daily. Disease Activity Index is scored every other day using the following criteria:

Weight Loss (%):

0 = ≤ 2%

1 = 3 to 6%

2 = 7 to 12%

3 = > 12%

Stool Consistency:

0 = Normal Stool (well-formed pellets)

1 = Semi-solid Stool

2 = Loose to Pasty Stool (does not adhere to the anus)

3 = Diarrhea (liquid stool that adhered to the anus)

Occult/Gross Blood (Using Hemoccult Test):

0 = Normal

1 = Positive Test

2 = Gross Blood in Stool

3 = Rectal Bleeding

At necropsy, the entire colon is harvested from each rat and assessed for evidence of blood or blood-tinged fluid for evaluation of colon content scores. Colon content is scored according to the following criteria:

Gross Scoring Criteria:

0 = Normal, no blood observed

1 = Semi-solid stool

2 = Semi-solid stool, may be slightly blood tinged

3 = Fluid stool with definite evidence of blood

4 = Bloody fluid

5 = No content, (include animals with no observable distal content in this category)

Histopathological Assessment

The colon is cut into Proximal and Distal halves and collected for processing and embedding. Each half is sectioned into 3 equidistant pieces and these sections are stained to quantitate inflammation, gland loss and epithelial loss (hematoxylin & eosin), which are scored according to these methods.

Sample Data (Click on Image to Enlarge):

Representative Photomicrographs of colons

For additional examples of positive controls, please contact us.

Notes:

Compounds that are effective in the treatment of human IBD have activity in this model and it is being used to investigate potential new therapies.

Optional Endpoint

  • PK/PD blood collections
  • Cytokine/chemokine analysis via Luminex(R)
  • Other sandwich ELISAs
  • CBC/clinical chemistry analysis
  • Soft tissue collection
  • Histopathologic analysis
  • Immunohistochemistry analysis
  • Disease Activity Index (DAI)
  • Endoscopy

References:

  1. Shi X, Winston JH, Sarna SK. Differential immune and genetic responses in rat models of Crohn’s colitis and ulcerative colitis. Am J Physiol Gastrointest Liver Physiol 2011; 300:G41–G51.
  2. Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol 2002; 20:495–549.
  3. Faure M, Mettraux C, Moennoz D, et al. Specific amino acids increase mucin synthesis and microbiota in dextran sulfate sodium-treated rats. J Nutr 2006; 136:1558–1564.
  4. Woodruff SA, Masterson JC, Fillon S, et al. Role of eosinophils in inflammatory bowel and gastrointestinal diseases. JPGN 2011; 52(6): 650–661.
  5. Arslan G, Erichsen K, Milde AM, et al. No protection against DSS-induced colitis by short-term pretreatment with seal or fish oils in rats. Integr Med Insights 2007; 2: 25–34.

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