Healthy Detoxification (Figure 1, left)Detoxification processes occur throughout the body. A healthy detoxification pathway typically involves three phases. Phase I involves oxidative activation of a toxin. This prepares the toxin for conjugation to a hydrophilic bio-molecule in Phase II. The conjugate is then moved through a series of Phase II transporters, leading to intestinal or kidney excretion.Impaired Detoxification (Figure 1, right)Intestinal inflammation disrupts detoxification in two ways.Inhibiting the conjugation of toxins throughout the body and inhibiting transport of toxins into the intestines. Intestinal inflammation down-regulates Phase II transporters. When transporters down-regulate, Phase I activity, which is coupled to Phase III, is also turned down. Phase I activity, however, does not get down-regulated. Phase I oxidation continues but is no longer coupled to Phase I conjugation.Inhibiting glutathione activity in the intestines. Phase II transporters bring glutathione (GSH) into the intestines from the liver. GSH is the primary anti-oxidant for quenching free-radical reactions in the intestines. A deficiency of GSH is a symptom of inflammatory bowel diseases, including Crohn's Disease. Thus down-regulation of Phase II transporters can be self-propagating as oxidative stress stops the flow of this crucial antioxidant.Recent research at the Nestle Cancer Center in Switzerland examined genetic expression of the body's detoxification pathways and found that the small intestine and the liver work together to coordinate detoxification and metabolism. The Nestle Center also found that glutathione activity is predominantly modulated from the small intestine. This finding supports our model of Phase II transporters in the intestines controlling Phase I pathways and points to the centrality of the intestines in any detoxification protocol.
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