Gastro-intestinal models

 

In addition to being an indication area itself for drugs, gastro-intestinal studies form an important part of the safety assessments. he majority of medicines are administered by oral ingestion and therefore must pass through the GI tract in order to be absorbed. As the GI tract is exposed to a far higher concentration of the PO administered compound than any other organ system, new compounds are often capable of causing stomach irritation, diarrhea, nausea and other GI symptoms. Stomach lesions, such as ulcerations and inflammations, are relatively common side effects of drugs.

Disturbances of the GI tract are easily observed and usually manifested as vomiting, excessive salivation, or changes in faeces (soft stool, diarrhea, absence of stool, bloody stool). These effects will be often result in changes in blood and urine electrolytes due to fluid loss.

Our gastro-intestinal models

In the gastro-intestinal area, we provide our customers with models for assessing both the efficacy and safety of compounds. Monitored parameters can include e.g. gastric mucosal damage (stomach and small and large intestine), different gut hormones (e.g. insulin, amylin, ghrelin, leptin, GLP-1 and PYY), food and water intake and urinalysis. However, since majority of our in vivo studies are tailored to each project and compound, we can easily adopt also other monitored parameters.

We provide the following models

  • Ulcerogenic potential
  • Charcoal propulsion
  • Gastric emptying
  • Gastric irritation
  • Chron’s disease (inflammatory bowel disease)

Inflammatory bowel disease, ulcerative colitis and Crohn disease

Dextran sodium sulfate (DSS)-induced colitis is one of the most frequently used rodent models for inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn disease (CD). The etiology of both UC and CD still remains largely unclear. It is suggested that a combination of genetic susceptibility factors and altered immune response driven by microbial factors in the enteric environment help the progress of the initiation and prolong of IBD. The acute DSS colitis model in susceptible mice strains is particularly useful to study the contribution of innate immune mechanisms of colitis. Dextran sodium sulphate-induced mice indicates the most comprehensive signs of the disease; significantly decreased body weight, change in faeces consistency toward diarrhea, increased faecal blood and colon weight/length ratio, and higher ACI. In conclusion, DSS-induced colitis can be used as a relevant model for the translation of mice data to human disease.

ACI - Average Colitis Index
The Average Colitis Index (ACI) is calculated, including the body weight, faeces consistency and faecal blood. Experimental groups were compared to healthy controls that were access to normal tap water. The results were evaluated statistically.

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Gastric ulceration – induced by EtOH or HCl

Intragastric administration of irritants leads to alteration of the gastric mucosa and gastric ulceration. Our ethanol or hydrochloric acid induced gastric ulceration model is used to asses the efficacy of the new compounds to prevent gastric ulceration in conscious rats.
Please follow this link to retrieve a detailed fact sheet of the EtOH or HCl induced gastric ulceration model

Gastric ulceration – induction by indomethacin or acetylsalisylic acid

Inhibition of prostaglandin synthesis by anti-inflammatory drugs is known to provoke gastric ulceration. In this model, the gastric ulceration is induced by indomethacin or acetylsalisylic acid and the model is used to assess the efficacy of the new compound to prevent this induced gastric ulcerations.

Please follow these links to retrieve a detailed fact sheet of our gastric models or to request a quote.
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