Detoxification

We are constantly being exposed to materials that interfere with cellular processes or that are poisonous. Such materials are described as "toxic" and are generally termed toxins. Some toxins are naturally occurring substances. These may be produced by plants or animals as a means of discouraging other organisms from destroying or eating them. Some toxins are dangerous to most other organisms, others are selective in their effect.

Increasingly, the toxins in our environment are chemicals introduced as a result of industrial processes or as part of products that we buy. There is an enormous, and growing, number of these compounds, and we are producing and using these substances in larger and larger amounts. Ranging from fertilizers and insecticides used in agriculture, to chemicals and solvents used in manufacturing, to plastics, packaging materials, dyes, food additives, and a host of other materials that we have in our homes, handle, and eat on a daily basis. Various drugs and pharmaceutical products are also potentially toxic. Indeed, in many instances it is their toxicity that makes them useful.

In many instances, the potential toxicity of new chemicals and compounds is unknown. However, if they are useful in some part of our economy, they are being produced and released in very large quantities. It is not an overstatement that we are currently running a massive experiment, asking in a rather crude

way whether the natural systems, and nature itself, can tolerate, eliminate, or in some other way manage these substances.

Organisms, including humans, have a complex system of enzymes that act on substances that are not a part of our normal metabolic system. These systems are not well understood. The chemicals and substances that they affect, the reactions that they carry out, and the products they produce are largely unknown.

A major portion of this system is built into a complex membrane system within each cell called the "smooth endoplasmic reticulum." Endoplasmic indicates that the membrane is contain in the cell space outside of the nucleus, and reticulum suggests that the membrane system is a complex web of fine tubular structures. The membrane system is described as smooth to distinguish it from the rough endoplasmic reticulum, the site of much of the cells protein synthesis machinery. The smooth endoplasmic reticulum (SER) contains a large number of different enzymes. Among these is a group of enzymes that absorb light of particular frequencies, and are known as "cytochrome p450" enzymes ("cyto" for cell, "chrome" for color).

There are a number of p450 cytochromes. While they are different enzymes they share a common activity, that of adding oxygen (or otherwise oxidizing) the compounds that they modify. There

are a number of different oxidation mechanisms and each cytochrome appears to act on a different set of compounds. While much is unknown, the alteration of compounds by the p450 cytochromes changes their chemical nature, and thus their toxicity to cells.

In many instances, cytochrome induced oxidation destroys or diminishes the toxicity of a compound. However, in some cases, cytochrome action may actually produce or increase toxicity. Indeed, some drugs are ineffective until they are activated by the p450 system. The general, if not universal, effect of p450 action is to alter a compound in a way that makes it possible for the body to eliminate it from the body. Elimination is frequently carried out by the kidneys and the compound appears in the urine, hence the common use of urine samples in drug testing.

Once again, the liver plays a central role. Liver cells have very highly developed SER and contain a large proportion of the body's p450 cytochromes. They also have a rich blood supply with good access to circulating compounds and ability to release modified compounds into the blood. While effective, the liver's ability to detoxify chemicals is limited. Chronic exposure to some toxins, such as alcohol, leads to liver disease and can cause death from liver failure. Similarly, the liver can be damaged by brief exposure to high levels of some organic compounds.