Xenobiotic Distribution: A Comprehensive Review and Toxicological Implications
DOI:
https://doi.org/10.64074/99wreq81Keywords:
Xenobiotics, Biosphere, Antibiotics, Carcinogens, Drugs, Environmental pollutants, Food additives, Hydrocarbons, PesticidesAbstract
Xenobiotics is derived from the Greek words ‘Xenos’, meaning foreign and strange, and ‘bios’, which means life. Concerning the environment, xenobiotics can be defined as chemically synthesized compounds that do not occur in nature and thus are ‘foreign’ to the biosphere. Relating to the organisms, a xenobiotic is any substance foreign to life/living organism. Thus, a xenobiotic is a foreign chemical substance found within an organism that is not naturally produced by or expected to be present within the organism. The definition of xenobiotics as compounds ‘foreign to life’ exhibiting unnatural structural features does not necessarily mean that they are toxic compounds, but many are indeed harmful to living organisms. Specifically, drugs such as antibiotics are xenobiotics are xenobiotics because the human body does not produce them itself, nor are they part of a normal food. Natural compounds can also become xenobiotics if another organism takes them up. The body removes xenobiotics by xenobiotic metabolism, which consists of their deactivation and excretion, which happens mostly in the liver. Enzymes are involved in the metabolism of xenobiotics. Excretion routes are urine, feces, breath, and sweat. Xenobiotics may be grouped as carcinogens, drugs, environmental pollutants, food additives, hydrocarbons, and pesticides.
References
Abernathy, D. and Flockhart, D.A. (2000): Molecular basis of cardiovascular drug metabolism implications for predicting clinically important drug interactions. Circulation .101:1749-1753.
Benet, L.Z., Mitchell, J.R. and Sheiner, L.B. (1990): Pharmacokinetics : The dynamics of drug absorption, distribution and elimination. In: The Pharmacological Basis of Therapeutics, A Goodman Gilman, TW Rall, AS Nies, and P Taylor (eds). Pergamon Press, Oxford, pp. 1-32.
Boberg, E.W., Miller, E.C., Miller, J.A., Poland, A. and Liem, A. (1983): Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1’-sulfooxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1’-hydroxysafrole in mouse liver. Cancer Res. 43: 5163-5173.
Brittebo, E.B. (1993): Metabolism of xenobiotics in the nasal olfactory mucosa: implications for local toxicity. Pharmacol Toxicol .72 Suppl 3:50-52.
Burchell, B. and Coughtrie, M.W.H. (1992): UDP-glucuronosyltransferases. In: Pharmacogenetics of Drug Metabolism, W Kalow (ed). Pergamon Press, New York, pp. 195-225.
Caldwell, J. (1993): Biochemical basis of toxicity. In: General and Applied Toxicity, BC Ballantyne, T Marrs, and P Turner (eds). MacMillan, London, pp. 165- 178.
Callaghan, R., Crowley, E. and Potter, S. (2008): P-glycoprotein: so many ways to turn it on. J Clin Pharmacol . 48:365-378.
Chinn, L.W. and Kroetz, D.L. (2007): ABCB1 pharmacogenetics: progress, pitfalls, and promise. Clin Pharmacol Ther .81:265-269.
Farabee, M. (2009): OnLine Biology Book. Vol. 2009; http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookTOC.html. Retrieved 25-01-2017.
Hladky, S.B. (1990): Pharmacokinetics. Manchester University Press, Manchester, New York.
Ho, R.H. and Kim, R.B. (2005): Transporters and drug therapy: Implications for drug disposition and disease. Clin Pharmacol Ther .78:260-277.
Josephy, D., Guengerich, P. and Miners, J.O. (2005): “Phase I and Phase II” drug metabolism: Terminology that we should phase out? Drug Metab Rev; 37:575-580.
Kalgutkar, A.S., Gardner, I. and Obach, R.S. et al., (2005): A comprehensive listing of bioactivation pathways of organic functional groups. Curr Drug Metab.6:161-225.
Kim, R.B. (2002): Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev .;34:47-54.
Koymans, L., Donne-Op Den Kelder, G.M., Koppele- Te, J.M. and Vermeulen, N.P.E. (1993): Cytochrome P450 their active site structure and mechanism of oxidation. Drug Met. Rev. 25: 325-388.
Kroncke, K.D., Fricker, G. and Meier, P.J. (1986): alpha-Amanitin uptake into hepatocytes. Identification of hepatic membrane transport systems used by amatoxins. J Biol Chem.;261: 12562-12567.
Lewis, D. (2000): On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics. Biochem Pharmacol. 60:293-306.
Lieber, C.S. (2005): Metabolism of alcohol. Clin Liver Dis;9:1-35.
Manahan, S. (2003): Toxicological Chemistry and Biochemistry . 3rd ed. New York: Lewis Publishers. Maryland, pp. 16-48.
Meijer, D.K.F. and Groothuis, G.M.M. (1991): Hepatic transport of drugs and proteins. In: Oxford Textbook of Clinical Hepatology, Vol. 1, N McIntyre, J Benhama, and H Bircher (eds). Oxford University Press, Oxford, pp. 40-78.
Miller, E.C. and Miller, J.A. (1947): The presence and significance of bound aminoazo dyes in the livers of rats fed p-demethylaminoazobenzene. Cancer Res;7: 468 - 480.
Nelson, D. (2004): Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice varients. Pharmacogenetics.14:1-18.
Pavek, P. and Dvorak, Z. (2008): Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Curr Drug Metab .9:129-143.
Price-Evans, D.A. (1993): N-acetyltransferase. In: Genetic Factors in Drug Therapy: Clinical and Molecular Pharmacogenetics. Cambridge University Press, Cambridge, pp. 211-285.
Timbrell, J. (2000): Principles of Biochemical Toxicology. 3rd ed. Philadelphia: Taylor & Francis. Pp. 321-330.
Timbrell, J.A. (1993): Biotransformation of xenobiotics. In: General and Applied Toxicology, Vol. 1, B Ballantyne, T Marrs, and P Turner (eds). Macmillan Press, New York, pp. 89-121.
Urquhart, B.L., Tirona, R.G. and Kim, R.B. (2007): Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: Implications for inter individual variability in response to drugs. J Clin Pharmacol .47:566-578.
Wallace, K.B. and Starkov, A.A. (2000): Mitochondrial targets of drug toxicity. Annu Rev Pharmacol Toxicol.40:353-388.
Wilce, M.C.J. and Parker, M.W. (1994): Structure and function of glutathione-S transferases. Biochem. Biophys. Acta 1205: 1-18.
Wilkinson, G.R. (1987): Clearance concepts in pharmacology. Pharmacol. Rev. 39: 1-47.
Williams, R.T. (1949): Detoxication Mechanisms: The Metabolism of Drugs and Allied Organic Compounds . 1st ed. London: Chapman and Hall; Pp. 23-32.
Williams, R.T. (1959): Detoxication Mechanisms: The Metabolism and Detoxication of Drugs, Toxic Substances, and Other Organic Compounds. 2nd ed. London: Chapman and Hall. Pp. 23-30.
Zamek-Gliszczynski, M.J., Hoffmaster, K.A. and Nezasa, K. et al., (2006): Integration of hepatic drug transporters and phase II metabolizing enzymes: Mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites. Eur J Pharm Sci.27:447-486.
