Foreign compounds

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reactions, classically referred to as phases one and two. Phase I is a functionalization of the lipophilic compound that can be used to attach a conjugate in Phase II. The conjugated product is usually sufficiently water-soluble to be excretable into the urine. The most important biotransformations of Phase I are aromatic and aliphatic hydroxylations catalyzed by cytochromes P450. Other Phase I enzymes are for example epoxide hydrolases or carboxylesterases. Typical Phase II enzymes are UDP-glucuronosyltrans-ferases, sulfotransferases, N-acetyltransferases and methyltransferases e.g. thiopurin S-methyltransferase. 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reaction, classically referred to as phases one and two. Phase I is a... 

Xenobiotic A foreign compound that has no role in the normal biochemistry of a living organism. A normal endogenous compound to one species can be a xenobiotic to another species. 

Smith, M. T., Thor, H., and Orrenius, S. (1983). The role of lipid peroxidation in the toxicity of foreign compounds to liver cells, Biochem. Pharmacol., 32, 763-764. 

This biennial report is oriented strongly towards the chemical aspects It will be of special interest to workers in the fields of metabolic and toxicological evaluation of foreign compounds. This volume has a 10-year period of coverage 4SSpp 11 (X)... 

Smith, L.J., Houston, M. and Anderson, J. (1993). Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma. Am. Rev. Resp. Dis. 147, 1461-1464. Smith, L.L. (1986). The response of the lung to foreign compounds that produce free radicals. Ann. Rev. Physiol. 48, 681-692. 

R. R. Scheline, Metabolism of foreign compounds by gastrointestinal microorganisms, Pharmacol, Rev., 25,... 

T. E. Gram, The metabolism of xenobiotics by the mammalian lung, in Extrahepatic Metabolism of Drugs and Other Foreign Compounds (T. E. Gram, Ed.), S.P. Medical and Scientific Books, New York, 1980, pp. 159-209. 

As a rule it is best to avoid separation steps, such as extraction, that involve the addition of a compound not already present. The reason for this rule is that extra processing steps will be required to recover the foreign compound so it can be reused. This means it is a costly operation. Whenever possible the number of processing steps should be reduced, not increased. 

Tubular secretion is the transfer of substances from the peritubular capillaries into the renal tubule for excretion in urine. This process is particularly important for the regulation of potassium and hydrogen ions in the body it is also responsible for removal of many organic compounds from the body. These may include metabolic wastes as well as foreign compounds, including drugs such as penicillin. Most substances are secreted by secondary active transport. 

For example, it is to be noted that UDP-glucuronic acid which is formed in the tissues, is used not only for polysaccharide synthesis, but also for neutralization and removal of toxic and useless materials or foreign compounds from the organism. 

Hansen, K.T. and Stentoft, K. (1995) Characterization of benzazepine UDP-glucuronosyl-transferases in laboratory animals and man. Xenobiotica The Fate of Foreign Compounds in Biological Systems, 25,611-622. 

Oxidation is intimately linked to the activation of polycyclic aromatic hydrocarbons (PAH) to carcinogens (1-3). Oxidation of PAH in animals and man is enzyme-catalyzed and is a response to the introduction of foreign compounds into the cellular environment. The most intensively studied enzyme of PAH oxidation is cytochrome P-450, which is a mixed-function oxidase that receives its electrons from NADPH via a one or two component electron transport chain (10. Some forms of this enzyme play a major role in systemic metabolism of PAH (4 ). However, there are numerous examples of carcinogens that require metabolic activation, including PAH, that induce cancer in tissues with low mixed-function oxidase activity ( 5). In order to comprehensively evaluate the metabolic activation of PAH, one must consider all cellular pathways for their oxidative activation. 

Immunoassays are based on the ability of the immune system to produce a virtually unlimited variety of antibodies each with a high affinity for foreign compounds (immunogens like viruses, bacteria, proteins, and haptens). Analytically, this phenomenon can be exploited by detection of this immunoreaction using labeled antibodies or antigens (i.e., compounds that can be bound by antibodies). The equilibrium between antibody (Ab), antigen (Ag), and immune complex (Ab-Ag) may be expressed as ... 

Gillette, J.R. 1994. Commentary. Perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. I. Correlation of changes in covalent binding of reactivity metabolites with changes in the incidence and severity of toxicity. Biochem. Pharmacol. 23, 2785. 

Thakker DR, Yagi H, Levin W, et al. Polycyclic aromatic hydrocarbons metabolic activation to ultimate carcinogens. In Anders MW, ed. Bioactivation of Foreign Compounds. Orlando, FL Academic Press 1985 177-242. 

Dougherty, K.K., Spilman, S.D., Green, C.E., Steward, A.R. and Byard, J.L. (1980). Primary cultures of adult mouse and rat hepatocytes for studying the metabolism of foreign compounds. Biochem. Pharmacol. 29 2117-2124. 

Foreign compounds may also enter the gut by direct diffusion or secretion across the gut wall, elimination in the saliva, pH partitioning of bases into the low pH of the stomach, and elimination in the pancreatic juice. 

The detoxification and excretion of xenobiotics (i.e., foreign compounds, including diet-derived allelochemicals) involve a suite of highly complex processes that allow an organism to respond to its internal and external chemical environments. Suchmetabolic resistance involves the biochemical transformation... 

Yu SJ (1983) Induction of detoxifying enzymes by allelochemicals and host plants in the fall armyworm. Pestic Biochem Physiol 19 330-336 Yu SJ (1984) Interactions of allelochemicals with detoxification enzymes of insecticide-susceptible and resistant fall armyworms. Pestic Biochem Physiol 22 60-68 Yu SJ (1986) Consequences of induced foreign compound-metabolizing enzymes in insects. In Brattsten LB, Ahmad S (eds) Molecular aspects of insect-plant associations. Plenum, New York, pp 153-174... 

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