Related Experiment Video
Updated: Aug 13, 2025
Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice
Dongwoo Kim1, Ja Seol Koo1, Soon Ha Kim2
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Abstract:
Uncontrolled chronic inflammation and necrosis is characteristic of inflammatory bowel disease (IBD). This study aimed to investigate the effect of necrosis inhibitor (NI, NecroX-7) on a dextran sulfate sodium (DSS) induced chronic colitis model of mice. DSS was administered on days 1-5, and the NI was administered intraperitoneally (3 mg/kg, 30 mg/kg) on days 1, 3, and 5 as well as every other day during the first five days of a three-week cycle. Three cycles of administration were performed. Colitis was evaluated based on the disease activity index (DAI) score, colon length, and histological score. Reverse transcription polymerase chain reaction testing, the Western blot assay, and immunohistochemical staining were performed to determine inflammatory cytokine levels. The NI reduced body weight change and the DAI score. Colon length and the histological score were longer and lower in the NI-treated groups, respectively. The NI decreased the expression of pro-inflammatory cytokines, particularly in tumor necrosis factor alpha (TNF-α) and phosphorylated nuclear factor kappa B (p-NF-κB). Immunohistochemical staining revealed decreased inducible nitric oxide synthase (iNOS) and high mobility group box 1 (HMGB1) levels. Overall, the NI improved DSS induced chronic colitis by attenuating the mRNA expression of pro-inflammatory cytokines such as TNF-α. Therefore, NI use is a potential, novel treatment approach for IBD.
Insights
Necrosis inhibitor (NI) effectively reduced chronic inflammation and symptoms in a mouse model of inflammatory bowel disease (IBD). This novel treatment attenuated key inflammatory markers, offering a potential new therapy for IBD patients.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Inflammatory bowel disease (IBD) is characterized by uncontrolled chronic inflammation and necrosis.
- Current treatments for IBD often have limitations, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic potential of a necrosis inhibitor (NI, NecroX-7) in a dextran sulfate sodium (DSS)-induced chronic colitis mouse model.
- To evaluate the effect of NI on disease activity, colon damage, and inflammatory markers in chronic colitis.
Main Methods:
- A mouse model of chronic colitis was established using DSS administration.
- Necrosis inhibitor (NI, NecroX-7) was administered intraperitoneally at different doses and schedules.
- Disease activity index (DAI), colon length, histological scores, and inflammatory cytokine levels (TNF-α, p-NF-κB, iNOS, HMGB1) were assessed.
Main Results:
- NI treatment significantly reduced body weight loss and DAI scores in DSS-induced colitis mice.
- NI administration led to increased colon length and improved histological scores compared to controls.
- NI decreased the mRNA and protein expression of pro-inflammatory cytokines, including TNF-α and p-NF-κB, and reduced iNOS and HMGB1 levels.
Conclusions:
- Necrosis inhibitor (NI) demonstrates significant efficacy in ameliorating DSS-induced chronic colitis in mice.
- NI attenuates key inflammatory pathways, including TNF-α signaling and pro-inflammatory cytokine production.
- NI represents a promising novel therapeutic agent for the management of inflammatory bowel disease (IBD).
