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Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
Prevention of chronic experimental colitis induced by dextran sulphate sodium (DSS) in mice treated with FR91
Valter R M Lombardi1, Ignacio Etcheverría, Iván Carrera
1Euroespes Biotechnology, Department of Cellular Immunology, A Coruña, Spain.
Abstract:
One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC). However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS). Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.
Insights
FR91, a microbial lysate, shows potential as a chemopreventive agent. It reduced inflammation and histological damage in a mouse model of dextran sulfate sodium (DSS)-induced colitis, suggesting a role in preventing intestinal inflammation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Chemotherapy faces challenges like drug toxicity and resistance, driving the search for novel cancer therapies.
- Microbial compounds offer a rich source for developing new antitumor drugs.
- Dextran sulfate sodium (DSS)-induced colitis in mice models human ulcerative colitis (UC), but its pathogenic factors remain unclear.
Purpose of the Study:
- To investigate the chemopreventive effects of FR91, a Bacillus-derived microbial lysate, against intestinal inflammation.
- To evaluate FR91's impact on histological changes in DSS-induced colitis in a mouse model.
Main Methods:
- Induction of colitis in mice using 2% dextran sulfate sodium (DSS) for 5 weeks.
- Evaluation of colonic mucosal morphology via hematoxylin-eosin staining and immunohistochemistry.
- Assessment of specific protein expressions (catenin-β, MLH1, APC, p53) and IFN-γ production.
Main Results:
- FR91 demonstrated immunomodulatory effects in the context of intestinal inflammation.
- The optimal dose of 20% FR91 showed no histological alterations or only mild lesions in DSS-induced colitis.
- Specific molecular markers associated with adenocarcinoma and dysplastic epithelium were observed.
Conclusions:
- FR91 exhibits potential as a chemopreventive agent against inflammation in DSS-induced colitis.
- The findings suggest FR91 may mitigate intestinal inflammation and associated pathological changes.
