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Fecal Excretion
Elimination of toxicants in the feces occurs from two processes, excretion in bile, which then enters the intestine, and direct excretion into the lumen of the gastrointestinal tract. The biliary route is an important mechanism for fecal excretion of xenobiotics and is even more important for the excretion of their metabolites. This route generally involves active secretion rather than passive diffusion. Specific transport systems appear to exist for certain types of substances, e.g., organic bases, organic acids, and neutral substances. Some heavy metals are excreted in the bile, e.g., arsenic, lead, and mercury. However, the most likely substances to be excreted via the bile are comparatively large, ionized molecules, such as large molecular weight (greater than 300) conjugates.
Once a substance has been excreted by the liver into the bile, and subsequently into the intestinal tract, it can then be eliminated from the body in the feces, or it may be reabsorbed. Since most of the substances excreted in the bile are water soluble, they are not likely to be reabsorbed as such. However, enzymes in the intestinal flora are capable of hydrolyzing some glucuronide and sulfate conjugates, which can release the less polar compounds that may then be reabsorbed. This process of excretion into the intestinal tract via the bile and reabsorption and return to the liver by the portal circulation is known as the enterohepatic circulation.
The effect of this enterohepatic circulation is to prolong the life of the xenobiotic in the body. In some cases, the metabolite is more toxic than the excreted conjugate. Continuous enterohepatic recycling can occur and lead to very long half-lives of some substances. For this reason, drugs may be given orally to bind substances excreted in the bile. For example, a resin is administered orally which binds with the dimethylmercury (which had been secreted in the bile), preventing reabsorption, and further toxicity.
The efficiency of biliary excretion can be affected by changing the production and flow of bile in the liver. This can occur with liver disease, which usually causes a decrease in bile flow. In contrast, some drugs (e.g., phenobarbital) can produce an increase in bile flow rate. Administration of phenobarbital has been shown to enhance the excretion of methylmercury by this mechanism.
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J. A. Timbrell, Principles of Biochemical Toxicology, Taylor & Francis LTD, London. |
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Another way that xenobiotics can be eliminated via the feces is by direct intestinal excretion. While this is not a major route of elimination, a large number of substances can be excreted into the intestinal tract and eliminated via feces. Some substances, especially those which are poorly ionized in plasma (such as weak bases), may passively diffuse through the walls of the capillaries, through the intestinal submucosa, and into the intestinal lumen to be eliminated in feces. Intestinal excretion is a relatively slow process and therefore, it is an important elimination route only for those xenobiotics that have slow biotransformation, or slow urinary or biliary excretion. Increasing the lipid content of the intestinal tract can enhance intestinal excretion of some lipophilic substances. For this reason, mineral oil is sometimes added to the diet to help eliminate toxic substances, which are known to be excreted directly into the intestinal tract.
 
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