Epithelial tissues gastrointestinal tract

Compounds in animal diets can exert their effects in the gastrointestinal tract or after absorption through the gut epithelial tissue into the bloodstream, or both. On some occasions the administered compounds may be applied topically (Table 1). 

The following methods can be used to determine the permeability of a drug substance from the gastrointestinal tract (1) in vivo intestinal perfusion studies in humans (2) in vivo or in situ intestinal perfusion studies using suitable animal models (3) in vitro permeation studies using excised human or animal intestinal tissues or (4) in vitro permeation studies across a monolayer of cultured epithelial cells. 

Inflammatory influences. Inflammation (p. 1211), which usually accompanies infection and can also arise from allergic responses, is affected by many substances.2293-6 These include chemotactic factors that attract neutrophils and monocytes2220 2294 and the adhesion molecules that assist in the movement of lymphocytes. 229e/f Some epithelial tissues, such as the mucosal surfaces of the gastrointestinal tract, are maintained in a continuous very low level of inflammation. This reflects the balance between activation of the immune system and inhibition of the system by signals from microorganisms both pathogenic and commensal 229 h... 

A consequence of the lower levels of plasma RBP produced by protein malnutrition is impairment of vitamin A transport from the liver to other tissues however, vitamin A deficiency can also result from heavy reliance on foods that are extremely poor sources of vitamin A, such as rice or cassava. Both factors (lack of RBP or of vitamin A) can lead to deterioration of the epithelial cells of the gastrointestinal tract, respiratory tract, and eye, all signs of vitamin A deficiency. Another sign is nightblindness. Table 4.19 illustrates how feeding protein to malnourished children can result in an improvement in vitamin A status, even when the source of proteins contains little or no vitamin A. Some children with kwashiorkor were fed skim milk. The concentrations of RBP and vitamin A measured in the serum of these children before and after feeding show an increase in plasma RBP. A dramatic rise in plasma vitamin A also occurred, probably as a result of the liver s... 

While the mechanism involved in vitamin A action in relation to carcinogenesis remains to be elucidated, several possibilities have been suggested. For example, vitamin A deficiency may act primarily on metabolic activation of carcinogens such deficiency may facilitate interaction of ultimate carcinogen with DNA. Finally, vitamin A is required in the differentiation of epithelial cells important in both respiratory and gastrointestinal tracts, and its deficiency may affect transformation of epithelia and thus predispose the tissue to neoplastic changes. 

Studies of animals exposed for life to formaldehyde in air or drinking water also show that formaldehyde primarily damages tissue at portals-of-entry (i.e., the upper respiratory tract and the gastrointestinal tract) evidence for toxic effects at distant sites is less consistent. Replicated inhalation studies have shown that formaldehyde induced malignant nasal tumors in rats at high exposure concentrations (10-15 ppm) that also induced nasal epithelial necrosis and cellular proliferation, but not at lower concentrations (0.3-2 ppm) that did not markedly damage nasal epithelial tissue (Albert et al. 1982 ... 

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