Localized Rectal Dextran Sulfate Sodium-Induced Colitis Is Associated with Small-Intestinal Shortening and Gut-Liver...

Area of Science:

• Gastroenterology
• Inflammatory Bowel Disease Research
• Animal Models of Disease

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon.
• Existing dextran sulfate sodium (DSS)-induced UC models often use oral administration, leading to widespread exposure and complicating extracolonic organ assessment.
• A need exists for a localized UC model to better study colon-specific inflammation and its systemic impact.

Purpose of the Study:

• To establish a localized ulcerative colitis (UC) model in rats via rectal administration of dextran sulfate sodium (DSS).
• To evaluate if this rectal DSS approach reduces direct DSS exposure to the small intestine and liver compared to oral models.
• To assess the impact of this localized inflammation on small intestinal morphology, hepatobiliary function, and the efficacy of 5-aminosalicylic acid treatment.

Main Methods:

• Rats were administered 40% DSS rectally for 13 days.
• Monitoring included body weight, Disease Activity Index (DAI), and histological scoring.
• Evaluated small intestinal morphology, inflammatory markers, bile flow, and hepatic bile salt export pump mRNA levels.
• Assessed the effects of 5-aminosalicylic acid treatment.

Main Results:

• Rectal DSS successfully induced localized distal colon and rectal inflammation, mirroring UC features like weight loss and mucosal injury.
• 5-aminosalicylic acid partially alleviated some DSS-induced effects.
• The small intestine showed shortening without inflammatory cell infiltration or increased cytokines.
• DSS treatment led to decreased bile flow and hepatic bile salt export pump expression, indicating hepatobiliary dysfunction.

Conclusions:

• The rectal DSS administration model provides a controlled and reproducible method for inducing colon-specific inflammation.
• This localized model overcomes limitations of oral DSS models, facilitating extracolonic organ evaluation.
• The model serves as a valuable research basis for studying inter-organ interactions, gut-liver axis dysfunction, and drug absorption in UC.