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Reactive Intermediate Formation

  • Chang-Hwei Chen
Chapter

Abstract

Some foreign compounds are acutely or potentially toxic, and others initially exhibit no intrinsic toxicity, but become harmful after metabolic conversion. Although foreign compound-metabolizing enzymes aim to produce water soluble metabolites, facilitating the excretion of foreign compounds from the body, however in many cases, metabolic conversion produces reactive intermediates. As a result of this, many toxic effects of foreign compounds do not result from the parent compounds, instead from reactive intermediates or metabolites that are formed inside cells.

Keywords

Reactive Oxygen Species Reactive Intermediate Metabolic Intermediate Metabolic Conversion Protein Adduct 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Bibliography

  1. Amacher DE (2006) Reactive intermediates and the pathogenesis of adverse drug reactions: the toxicology perspective. Curr Drug Metab 7:219–229PubMedCrossRefGoogle Scholar
  2. Anders MW (1985) Bioactivation of foreign compounds. Academic Press, New YorkGoogle Scholar
  3. Anders MW (2007) Chemical toxicology of reactive intermediates formed by the glutathione-dependent bioactivation of halogen-containing compounds. Chem Res Toxicol 21:145–159PubMedCrossRefGoogle Scholar
  4. Baird WM, Hooven LA, Mahadevan B (2005) Carcinogenic polycyclic aromatic hydrocarbon–DNA adducts and mechanism of action. Environ Mol Mutagen 45:106–114PubMedCrossRefGoogle Scholar
  5. Boelsterli UA (2007) Mechanistic toxicology. CRC, Boca RatonGoogle Scholar
  6. Bogdanffy MS, Taylor ML (1993) Kinetics of nasal carboxylesterase-mediated metabolism of vinyl acetate. Drug Metab Dispos 21:1107–1111PubMedGoogle Scholar
  7. Chandrasekara A, Shahidi F (2011) Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species. J Agric Food Chem 59:428–436PubMedCrossRefGoogle Scholar
  8. Dekant W, Vamvakas S (1993) Glutathione-dependent bioactivation of xenobiotics. Xenobiotica 23:873–887PubMedCrossRefGoogle Scholar
  9. Eaton DL, Gallagher EP (1994) Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol 34:135–172PubMedCrossRefGoogle Scholar
  10. Glatt H (2000) Sulfotransferases in the bioactivation of xenobiotics. Chem Biol Interact 129:141–170PubMedCrossRefGoogle Scholar
  11. Guengerich FP (2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 14:611–650PubMedCrossRefGoogle Scholar
  12. Hinson JA, Forkert PG (1995) Phase II enzymes and bioactivation. Can J Physiol Pharmacol 73:1407–1413PubMedCrossRefGoogle Scholar
  13. James LP, Capparelli EV, Simpson PM et al (2008) Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose. Clin Pharmacol Ther 84:684–690PubMedCrossRefGoogle Scholar
  14. Kalgutkar AS, Dalvie DK, O’Donnell JP et al (2002) On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics. Curr Drug Metab 3:379–424PubMedCrossRefGoogle Scholar
  15. Kim SY, Suzuki N, Laxmi YR et al (2004) Genotoxic mechanism of tamoxifen in developing endometrial cancer. Drug Metab Rev 36:199–218PubMedCrossRefGoogle Scholar
  16. Koob M, Dekant W (1991) Bioactivation of xenobiotics by formation of toxic glutathione conjugates. Chem Biol Interact 77:107–136PubMedCrossRefGoogle Scholar
  17. Levi PE, Hodgson E (2008) Reactive metabolites and toxicity. In: Smart RC, Hodgson E (eds) Molecular and biochemical toxicology. Wiley, New YorkGoogle Scholar
  18. MacKenzie EL (2008) Reactive oxygen/metabolites and toxicity. In: Smart RC, Hodgson E (eds) Molecular and biochemical toxicology. Wiley, New YorkGoogle Scholar
  19. McLemore TL, Litterst CL, Coudert BP et al (1990) Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines. J Natl Cancer Inst 82:1420–1426PubMedCrossRefGoogle Scholar
  20. Parkinson A, Ogilvie BW (2008) Biotransformation of xenobiotics. In: Klaassen CD (ed) Casarett and Doull’s toxicology: the basic science of poisons. McGraw-Hill, New YorkGoogle Scholar
  21. Perlow RA, Kolbanovskii A, Hingerty BE et al (2002) DNA adducts from a tumorigenic metabolite of benzo[a]pyrene block human RNA polymerase II elongation in a sequence- and stereochemistry-dependent manner. J Mol Biol 321:29–47PubMedCrossRefGoogle Scholar
  22. Raucy JL, Kraner JC, Lasker JM (1993) Bioactivation of halogenated hydrocarbons by cytochrome P4502E1. Crit Rev Toxicol 23:1–20PubMedCrossRefGoogle Scholar
  23. Ritter JK (2000) Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions. Chem Biol Interact 129:171–193PubMedCrossRefGoogle Scholar
  24. Shimada T (2006) Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet 21:257–276PubMedCrossRefGoogle Scholar
  25. Smith BJ, Curtis JF, Eling TE (1991) Bioactivation of xenobiotics by prostaglandin H synthase. Chem Biol Interact 79:245–264PubMedCrossRefGoogle Scholar
  26. Stadtman ER (2006) Protein oxidation and aging. Free Radic Res 40:1250–1258PubMedCrossRefGoogle Scholar
  27. Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Biomedical SciencesUniversity at Albany, State University of New YorkAlbanyUSA

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