Crohn's disease (CD) is a chronic condition observed in human and animal species affecting the gastrointestinal tract. It is one of the forms of Inflammatory Bowel Disease (IBD) complex, while the other being Ulcerative Colitis (UC). Animal models for experimental replication of IBD can be spontaneous, induced, or through genetic manipulations. Of these models, chemically induced models are favored due to the economic, ease of working and repeatability. For preclinical evaluation of anti-inflammatory agents, Creative Biolabs offers chemically-induced IBD models, such as indomethacin-induced small intestinal inflammatory model.
Indomethacin-Induced Adverse Effects
Indomethacin is a nonsteroidal drug with anti-inflammatory, anti-pyretic and analgesic properties. It is commonly used to decrease the fever, pain and other effects caused by inflammation. While NSAIDs are widely used in clinical medicine, their use is reported to be associated with a broad spectrum of adverse reactions, including increased intestinal permeability, the reduction of intestinal mucus and microcirculatory disturbances accompanying abnormally increased intestinal motility. These changes allow luminal substances, such as bile acid and intestinal bacteria, access to the mucosa, thereby leading to inflammation through infiltration of neutrophils, upregulation of inflammatory cytokines, and the production of reactive oxygen species.
Features of Indomethacin-induced IBD Model
Several advantages of indomethacin-induced IBD model support it as an appropriate model for Crohn's Disease research and for new drug or therapy investigation:
Induction of Small-intestinal Lesions
Typically, intestinal injury can be induced in rats by two 24-h apart subcutaneous injections of indomethacin. After the induction of intestinal injury, mucosal permeability can be evaluated using FITC-labeled dextran or phenolsulphonphthalein (PSP). After the rat is sacrificed, the small intestine can be removed and cut for measurement of mucosal lesion area and histopathological assessment under a microscope. Moreover, intestinal inflammation score, myeloperoxidase (MPO) activity, cytokine production can be determined.
Fig.1 Microscopic picture in sections obtained from ileo-caecal region in healthy rats(A) and indomethacin treated rats (B). (Vemu et al. 2015)
For assessing the effect of mucosal protective drugs or anti-inflammatory drugs on the small intestinal mucosal injury, various assessments can be performed, including but not limited to:
Meanwhile, Creative Biolabs also offers other types of rodent digestive system disease models that you may be interested in. They are listed as follows for you to review:
Creative Biolabs is known as a leading non-clinical CRO for preclinical drug development. We help to choose the most validated and reliable models for testing your compounds and our years of experience can help guide your decision regarding the best model for your application. In addition, we work together with our clients to develop new animal models tailored to their specific pharmaceutical screening and evaluation programs. Contact us for more information or a formal quote.
Reference
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