Of 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... 

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)... 

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

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. 

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. 

Nebert, D.W. and Felton, J.S. Importance of genetic factors influencing the metabolism of foreign compounds. Fed. Proc. (1976) 35 1133-1141. 

D. R. Thakker, H. Yagi, W. Levin, A. W. Wood, A. H. Conney, D. M. Jerina, Polycyclic Aromatic Hydrocarbons Metabolic Activation to Ultimate Carcinogens , in Bioactivation of Foreign Compounds , Ed. M. W. Anders, Academic Press, Orlando, 1985, p. 177 - 242. 

Glutathione as a sulfur nucleophile in the metabolism of foreign compounds... 

Parke DV. 1968. The biochemistry of foreign compounds. Oxford, England Pergamon Press, 224. 

PI. Parke, D. V., The Biochemistry of Foreign Compounds. Pergamon, Oxford, 1968. 

Renal elimination of foreign compounds may change dramatically with increasing age by factors such as reduced renal blood flow, reduced glomerular filtration rate, reduced tubular secretory activity, and a reduction in the number of functional nephrons. It has been estimated that in humans, beginning at age 20 years, renal function declines by about 10% for each decade of life. This decline in renal excretion is particularly important for drugs such as penicillin and digoxin, which are eliminated primarily by the kidney. 

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