An improved rat model for chronic inflammatory bowel disease

Ghattamaneni, Naga K. R. and Panchal, Sunil K. and Brown, Lindsay (2019) An improved rat model for chronic inflammatory bowel disease. Pharmacological Reports, 71 (1). pp. 149-155. ISSN 1734-1140


Background: Inflammatory bowel disease (IBD) is an important cause of chronic disability in humans.

Methods We characterized a model of chronic IBD in young male Wistar rats by administering dextran sodium sulfate (DSS: 0%, 0.25%, 0.5%, or 1% in drinking water) for six weeks, with 0.5% DSS for twelve weeks, following DSS cessation or together with treatment with sulfasalazine for the last 6 weeks. We measured gastrointestinal characteristics including stool consistency, blood in stools, small intestine and colon length, intestinal transit and permeability, and gut microbiota, as well as extra-intestinal parameters including oral glucose tolerance, systolic blood pressure, fat and lean mass, and left ventricular stiffness.

Results: At 6 weeks, 0.25-1% DSS produced gastrointestinal changes as diarrhea and blood in stools. At 12 weeks, 0.5% DSS produced chronic and sustained gastrointestinal changes, with marked infiltration of inflammatory cells throughout the gastrointestinal tract and crypt distortion. Firmicutes increased and Bacteroidetes and Actinobacteria decreased in DSS-treated rats. Changes were reversed by DSS cessation or sulfasalazine treatment. Gastrointestinal permeability and extra-intestinal parameters did not change, so DSS changes were limited to the gastrointestinal tract.

Conclusions: Chronic 0.5% DSS produces selective and reversible gastrointestinal changes, providing an improved chronic model in rats that mimics human IBD for testing new interventions.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Accepted version embargoed until 1 March 2020 (12 months), in accordance with the copyright policy of the publisher.
Faculty / Department / School: Current - Institute for Agriculture and the Environment
Date Deposited: 09 Jan 2019 05:05
Last Modified: 09 Jan 2019 05:05
Uncontrolled Keywords: Dextran sodium sulfate; inflammatory bowel disease; rats; sulfasalazine; methods
Fields of Research : 11 Medical and Health Sciences > 1111 Nutrition and Dietetics > 111103 Nutritional Physiology
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1016/j.pharep.2018.10.006

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