Understand what DSS is and how it incites inflammation
Chemically induced animal models of intestinal inflammation are commonly used because they are simple to induce and the onset, duration and severity of inflammation are immediate and controllable. Dextran sodium sulfate (DSS)-induced colitis has been used for over 2 decades in preclinical studies and to study Inflammatory Bowel Disease (IBD) pathogenesis.
DSS is a water soluble, negatively charged sulfated polysaccharide with a variable molecular weight ranging from 5 to 1400 kDa. It can be used in conjunction with other incitants or independently to induce colitis.
DSS is directly toxic to epithelial cells, causing erosions with complete loss of surface epithelium and increasing colonic mucosal permeability, allowing entrance of large molecules with molecular weights up to 50 kDa, including DSS.
Here’s a little more detail about what's going on inside the body:
Disrupting the epithelial barrier exposes the lamina propria to luminal contents and bacterial antigens, triggering the activation of inflammatory pathways and increasing the production of inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, etc.).
DSS-induced colitis is mediated by both Th1 and Th2 immune mechanisms, and several factors involved in innate immunity are also affected by DSS treatment—observed by changes in the expression of mediators of the innate immune system (e.g., MyD88, TLR4 and TLR9). Changes in these pathways contribute to epithelial cell damage and subsequent intestinal inflammation, making it possible to study IBD in several animal models such as mice, pigs, and zebrafish.
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Consider the factors influencing the effectiveness of DSS
The effectiveness of DSS towards inducing colitis depends on several factors:
- DSS dosage concentration
- Duration and frequency of administration
- Method of administration
- Molecular weight of the manufactured DSS
- Animal model, strain and gender
- Housing environment of animals
- Intestinal microbial environment
Factor |
Property |
Description |
DSS |
Molecular Weight |
40-50 kDa is necessary for tissue penetration. Larger DSS molecules do not penetrate the colonic tissue effectively and smaller molecules are poorly distributed. |
Concentration |
Generally, DSS dosage ranges from 1.5%-5%, with 1% producing mild symptoms. |
|
Frequency and duration of Administration |
The frequency and duration of DSS treatments depends on the study question and whether you are looking to induce acute or chronic colitis. Acute: ~5-7 day administration Chronic: 4-5 repeating cycles of DSS and sterile water for several weeks. |
|
Method of Administration |
For murine models, adding DSS to drinking water is common, however, there are several cases where rectal administration is more suitable. The daily water intake value for mice is 7~10 ml/day, and for rats is 11ml/100g body weight/day. |
|
Batch Consistency |
Consistency between batches/lots is critical for reproducibility. Choose a vendor that has robust quality control protocols in place to ensure the DSS you use remains within a certain molecular weight range. |
|
Animal Model |
Animal |
No animal is the perfect model for investigating IBD, and your choice of animal depends on your specific research question. Mouse models are the most commonly used, making them useful for comparison studies, whereas larger animals (e.g., pigs and primates) are more useful in evaluating the efficacy of potential experimental drugs prior to clinical trials. |
Gender |
Male mice are more susceptible to chemically induced colitis. Female mice are partially protected, potentially mediated by estradiol. |
|
Strain |
Certain strains are more susceptible to DSS colitis than other strains. Susceptible strains include C3H/HeJ, C57BL/6, BALB/C |
|
|
Environment |
Housing conditions |
Group versus individual housing units and the frequency of cage changes can dictate coprophagy behavior (and therefore intestinal microbiome) and the level of stress on the animal. |
Microbial environment |
The environment that animal models are raised in (e.g., germ-free versus pathogen-free versus wild-type) can influence the intestinal microbial environment. |
The ideal dosage depends on your study, animal model, and the genetic background of your animals. By adjusting the concentration and duration of DSS treatment, you can study the mechanisms involved in both acute and chronic inflammation. As an example, Rajendiran, et al. induced acute colitis in Wistar rats by administering 5% DSS in drinking water for 5 days and chronic colitis by administering 5% DSS for the first 9 days and 2% DSS for an additional 18 days.
As with any other experiment, keeping variables as consistent as possible will help bolster the reliability and reproducibility of results. Keep the animal habitat, diet and husbandry consistent and optimal.
ProTips
- 36,000-50,000 Da is the best molecular range of DSS for colitis model creation. Low molecular weight DSS has a weaker inflammatory effect, and higher molecular weight DSS will not absorb as easily.
- DSS is a polymer, and the range of molecular weight is only indicating an average value. Molecular weight varies from lot to lot, but MP Bio’s DSS always falls within the optimum range. We recommend purchasing enough of the same lot of DSS to cover your entire experimental project. If this is not feasible, we recommend performing a pre-test prior to switching lots.
- Prepare DSS solution with sterile water and refer to our application guide for detailed w/v concentration. 0.22 µm filtration is always recommended prior to use.
- Freshly prepare DSS solution every 1-2 days.
- In order to clearly observe model development, adequate housing needs to be provided; we recommend 2-3 per cage and no more than 5 per cage at maximum.
- Generally 2 days of treatment with DSS cause epithelial barrier destruction, and you can observe it on Day 3, Day 5, and Day 7. We suggest conducting a pathological examination throughout the course of treatment.
Related Articles:
- An Overview of DSS-Induced Colitis
- Animal Models of IBD
- FAQs about dextran sodium sulfate
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