Pharmaceutical, nutraceutical, food additive, and chemical companies need to know how their compounds affect the intestinal cell health. Chemicals entering the intestinal tract can affect the intestinal epithelium.
Compounds that enter the body by the oral route, enter the gastrointestinal tract (GIT). The GIT is a complex system that facilitates the digestion and absorption of food derived fats, carbohydrates, and proteins. The primary site of enzymatic breakdown and absorption is the upper portion of the small intestine (duodenum). Chemicals that enter the intestine via ingestion of medicines or food products are absorbed into the portal circulation and carried to the liver. During the absorption process compounds can undergo metabolism by Cytochrome P450 enzymes in the intestinal epithelium. Exogenous compounds can also induce inflammatory responses in the intestine or cause direct toxicity.
Critical functions of the gastrointestinal tract:
✓Break down food for use; Propulsion
✓Mechanical digestion; Chemical digestion
✓Nutrient absorption; Waste production
The effects of chemicals on human intestinal heath must be evaluated using an in vitro model that is physiologically relevant. Standard tumor derived intestinal cell lines, such as HT-29, Caco2, and HCT-8 have been used to understand permeability or specific mechanisms of chemical toxicity. However, these models do not provide the multiple cell layers, or the production of mucous that are present in vivo
. These components of the intestinal tract can have a tremendous influence on chemical toxicity and permeability.To address this issue the use of reconstructed human three dimensional tissues cultured at an air-liquid interface provides an excellent solution. A three dimensional tissue model has many of the physiological attributes of in vivo
Based on the questions being asked, IONTOX scientists will assist you in selecting the best in vitro
model for your study.
Advantages to working with IONTOX scientists to study intestinal toxicity.
✓Extensive experience with human 3D models
✓Able to obtain compound permeability data
✓Determine effects on key intracellular pathways
✓Choice of intestine model that best fits your research goals
✓Custom designed experimental protocols
When working with IONTOX your company can select a wide range of intestinal toxicity tests that can be utilized with a verity of different intestinal models. The question being asked will determine the best cell model for your application. The most in vivo
like model is EpiIntestinal™ (MatTek, Corp). This human reconstructed 3-dimensional tissue represents many key features of in vivo intestinal epithelium (see figure below). The tissue incorporates enterocytes, paneth cell, M cells, tuft cells and intestinal stem cells into a highly differentiated, polarized epithelium.
The EpiIntestinal™ tissue is cultured at the air-liquid interface (ALI), which enables physiological (luminal) exposures to occur. EpiIntestinal™ recapitulates many aspects of normal intestinal function including barrier, metabolism, inflammatory and toxicity responses, similar to native human intestinal tissue.
MatTek’s EpiIntestinal combined with the expertise of IONTOX scientists gives your company a precise understanding of compound permeability, metabolism, and inflammation processes in regards to the gastrointestinal tract (GIT).
In addition to using a 3-dimensional model for studying intestinal toxicity, your company can select from a variety of human cell lines including, Caco-2, HT-29, HT-29-MTX, and HCT8 (McKim et al., 2016). These cell lines are extremely useful when questions related to compound effects on a specific pathway are asked or when a larger number of compounds must be screened for relative effect and prioritization. When working with these models IONTOX scientists put half a century of experience and knowledge of the latest in vitro
technology to work for your business.
To request a quote for an in vitro
intestinal toxicity study fill out the contact form on iontox.com
or email firstname.lastname@example.org. All contact requests will be responded to within one to two business days.