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Molecular Aspects of Oxidative Drug Metabolizing Enzymes pp 515–532Cite as

Drug Metabolism, Lipid Peroxidation and Glutathione

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Part of the book series: NATO ASI Series ((ASIH,volume 90))

Abstract

Cytochrome P-450 (P450) mediated drug metabolism can be connected with the creation of free oxygen radicals such as superoxide radical anion (O .−2 ) and hydroxyl radical (OH.), and hydrogen peroxide (H2O2), so-called reactive oxygen species (ROS), by different ways and mechanisms. This is the beginning of a multistep chain mechanism (initiation, propagation and termination) in the further production of radicals and of peroxidation of lipids, proteins and DNA, leading finally to cell damage and cell death. The tripeptide glutathione (GSH) serves both as coupler in drug phase II metabolism to form glutathione conjugates and later on evtl. mercapturic acid derivatives, but also as radical scavenger, thus protecting liver parenchymal and other cells throughout the whole organism from damage. Thus there are different connections between the microsomal electron transport chain with P450 (with its functions as monooxygenase, oxidase and peroxidase) and GSH.

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References

  • Allen R C, (1986) Phagocytic leukocyte oxygenation activities and chemiluminescence: a kinetic approach to analysis. Methods in Enzymology 133: 449–493

    Article  PubMed  CAS  Google Scholar 

  • Archakov A I, Zhukov A A, (1989) Multiple activities of cytochrome P-450. In: Ruckpaul K, Rein H, (eds): Frontiers in biotransformation. Basis and mechanisms of regulation of cytochrome P-450. Akademie-Verlag Berlin, 1: 151–175

    Google Scholar 

  • Blanck J, Ristau O, Zhukov A A, Archakov A I, Rein H, Ruckpaul K, (1991) Cytochrome P-450 spin state and leakiness of the monooxygenase pathway. Xenobiotica 21: 121–135

    Article  PubMed  CAS  Google Scholar 

  • BriheimG, Stendahl O, Dahlgren C, (1984) Intra-and extracellular events in luminol- dependent chemiluminescence of polymorphonuclear leukocytes. Infect Immun 45: 1–5

    Google Scholar 

  • Coon M J, Vaz ADN, (1987) Radical intermediates in peroxide-dependent reactions catalyzed by cytochrome P-450. J Biosciences 11: 35–40

    Article  CAS  Google Scholar 

  • Cotgreave I A, Moldeus P, Orrenius S, (1988) Host biochemical defense mechanisms against prooxidants. Ann Rev Pharmacol Toxicol 28: 189–212

    Article  CAS  Google Scholar 

  • Csomós G, Fehér J, (eds)(1992) Free radicals and the liver. Springer Berlin Dahlgren C, Stendahl O (1983) Role of myeloperoxidase in luminol-dependent chemiluminescence of polymorphonuclear leukocytes. Infect Immun 39: 736–741

    Google Scholar 

  • Elsbach P, Weiss J (1983) A réévaluation of the roles of the O2-dependent and O2—independent microbial systems of phagocytes. Rev Infect Dis 5: 843–853

    Article  PubMed  CAS  Google Scholar 

  • Emerit I, Chance B, (eds)(1992) Free radicals and aging. Birkhäuser Basel

    Google Scholar 

  • Fehér J, Csomös G, Vereckei A, (eds) (1987) Free radical reactions in medicine. Springer Berlin

    Chapter  Google Scholar 

  • Frenkl R, Gyre A, Szeberenyi S, (1980a) The effects of muscular exercise on the microsomal enzyme system of the rat liver. Europ J Appl Physiol 44: 135–140

    Article  CAS  Google Scholar 

  • Frenkl R, Gyre A, Meszaros J, Szeberenyi S, (1980b) A study of the enzyme inducing effect of physical exercise in man. J Sports Med 20: 371–376

    CAS  Google Scholar 

  • Gyllenhammar H, (1987) Lucigenin chemiluminescence in the assessment of neutrophil superoxide production. J Immun Meth 97: 209–213

    Article  CAS  Google Scholar 

  • Halliwell B, Aruoma O I, (eds) (1993) DNA and free radicals.Ellis Horwood Chichester Harman D (1984) Free radicals and the origination, evolution, and present states of the free radical theory of aging. In: Armstrong D, Sohal R S, Cutler R G, Slater T F, (eds) Free radicals in molecular biology, aging, and disease, Raven Press New York, pp 1–12

    Google Scholar 

  • Kahl R, Weimann A, Weinke S, Hildebrandt A G, (1987) Detection of oxygen activation and determination of the activity of antioxidants towards reactive oxygen species by use of the chemiluminogenic probes luminol and lucigen. Arch Toxicol 60: 158–162

    Article  PubMed  CAS  Google Scholar 

  • Ketterer B, Taylor J B, (1990) Glutathione Transferases. In: Ruckpaul K, Rein H, (eds): Frontiers in biotransformation. Principles, mechanisms and biological consequences of induction. Akademie-Verlag Berlin, 2: 244–277

    Google Scholar 

  • Klinger W, Freytag A, Schmitt W, (1986) Influence of age, hexobarbital, and aniline on NADPH/NADH dependent hydrogen peroxide production in rat hepatic microsomes. Arch Toxicol, Suppl 9: 382–385

    Google Scholar 

  • Klinger W, Müller D, Kleeberg U, Jahn F, Glöckner R, (1987) Developmental pharmacology. In: Rand M J, Raper C, (eds) Pharmacology. Proceedings of the Xth International Congress of Pharmacology (IUPHAR), Sydney, 23–28 August 1987, pp 753–763

    Google Scholar 

  • Klinger W, (1990) Biotransformation of xenobiotics during ontogenetic development. In. Ruckpaul K, Rein H, (eds) Frontiers in Biotransformation. Principles, mechanisms and biological consequences of induction. Akademie-Verlag Berlin, 2: 113–149

    CAS  Google Scholar 

  • Kretzschmar M, Klinger W, (1989) Gamma-glutamytranspeptidase in liver homogenates of rats of different ages: enzyme kinetics and age course of Km and Vmax. Z.Versuchstierk. 32: 41–47

    CAS  Google Scholar 

  • Kretzschmar M, Glöckner R, Klinger W, (1990) Glutathione levels in liver and brain of newborn rats: investigations on the influence of hypoxia and reoxidation on lipid peroxidation. Physiol Bohemoslov 39: 257–260

    PubMed  CAS  Google Scholar 

  • Kretzschmar M, Klinger W (1990) The hepatic glutathione system - influences of xenobiotics. Exp Pathol 38: 145–164

    PubMed  CAS  Google Scholar 

  • Kretzschmar M, Bach G, Ratzmann I, Fleck C, Klinger W (1991a) Ontogenetic changes in hepatic glutathione system (synthesis, catabolism, export) of male Uje.Wist rats. J Exp Anim Sei 34: 132–139

    CAS  Google Scholar 

  • Kretzschmar M, Müller D, Hübscher J, Marin E, Klinger W, (1991b) Influence of aging, training and acute physical exercise on plasma glutathione and lipid peroxides in man. Int J sports Med 12: 218–222

    Article  PubMed  CAS  Google Scholar 

  • Kretzschmar M, Pfeifer U, Machnik G, Klinger W, (1992) Glutathione homeostasis and turnover in the totally hepatectomized rat: evidence for a high glutathione export capacity of extrahepatic tissues. Exp Toxic Pathol 44: 273–281

    Article  CAS  Google Scholar 

  • Kretzschmar M, Müller D, (1993) Aging, trainig and exercise. Sports Med 15: 196–209 Kretzschmar M, (1994) The role of free radicals in the pathophysiology. In: Vincent J L, Sprung C, Eyrich K, Reinhart K, (eds) Update in intense care and emergency medicine. Springer Berlin (in press)

    Google Scholar 

  • Kuthan H, Ullrich V, (1982) Oxidase and oxigenase function of the microsomal cytochrome P-450 monooxygenase system. Eur J Biochem 126: 583–588

    Article  PubMed  CAS  Google Scholar 

  • Müller-Peddinghaus R, (1984) In vitro determination of phagocyte activity by luminol- and

    Google Scholar 

  • lucigenin-amplified chemiluminescence. Int J Immunpharmac 6: 455–466

    Google Scholar 

  • Müller-Peddinghaus R, Wurl M, (1987) The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers. Biochem Pharmacol 36: 1125–1132

    Article  PubMed  Google Scholar 

  • Poli G, Albano E, Dianzani M U, (eds)(1993) Free radicals: from basic science to medicine. Birkhäuser Basel

    Google Scholar 

  • Premereur N, Van den Branden C, Roels F, (1986) Cytochrome P-450-dependent H2O2 production demonstrated in vivo. Febs 199: 19–22

    Article  CAS  Google Scholar 

  • Rao, P S, Luber J M, Milinowicz J, Lalezari P, Mueller H S, (1988) Specificity of oxygen radical scavengers and assessment of free radical scavenger efficiency using luminol enhanced chemiluminescence. Biochem Biophys Res Commun 150: 39–44

    Article  PubMed  CAS  Google Scholar 

  • Reuter A, Klinger W, (1992) The influence of systemic hypoxia and reoxygenation on the glutathione redox system of brain, liver, lung and plasma in newborn rats. Exp Toxic Pathol 44: 339–343

    Article  CAS  Google Scholar 

  • Sies H, Murphy M E, Di Mascio P, Stahl W, (1992) Tocopherols, carotenoids and the glutathione system. In: Ong ASH, Packer L, (eds) Lipid-soluble antioxidants: biochemistry and clinical applications. Birkhäuser Basel, pp 160–165

    Google Scholar 

  • Slater T F, Cheeseman K H, (eds)(1993) Free radicals in medicine. Brit Med Bull 49, No 3

    Google Scholar 

  • Southeron P A, Powis G, (1988) Free radicals in medicine. I. Chemical nature and biologic reactions. II. Involvement in human disease. Mayo Clin Proc 63: 381–408

    Google Scholar 

  • Spatz L, Bloom A D, (eds)(1992) Biological consequences of oxidative stress. Implications for cardiovascular disease and carcinogenesis. Oxford University Press New York/Oxford

    Google Scholar 

  • Tarr M, Samson F, (eds)(1993) Oxygen free radicals in tissue damage. Birkhäuser Basel

    Google Scholar 

  • Thomas H, Timms C W, Oesch F, (1990) Epoxide hydrdolase: molecular properties, induction, polymorphisms and function. In: Ruckpaul K, Rein H, (eds) Frontiers in Biotransformation. Principles, mechanisms and biological consequences of induction. Akademie-Verlag Berlin, 2: 278–337

    Google Scholar 

  • Uhlig S, Wendel A (1992) Minireview. The physiological consequences of glutathione variations. Life Sci 51: 1083–1094

    Google Scholar 

  • Vereckei A, Feher E, Bläzovics A, György J, Toncser H, Feher J (1992) Free radical reactions in the pathomechanism of amiodarone liver toxicity.In: Csomös G, Feher J, (Eds.): Free radicals and the liver, Springer Berlin etc. pp. 124–157

    Google Scholar 

  • Weimann A, Hildebrandt A G, Kahl R, (1984) Different efficiency of various synthetic antioxidants towards NADPH induced chemiluminescence in rat liver microsomes. Biochem Biophys Res Commun 25: 1033–1038

    Article  Google Scholar 

  • Williams A J, Cole P J, (1991) In vitro stimulation of alveolar macrophage metabolic activity by polystyrene in the absence of phagocytosis. Br J exp Path 62: 1–7

    Google Scholar 

Download references

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, Friedrich-Schiller-University of Jena, Loebderstr. 1, D-07743, Jena, Germany

    Wolfgang Klinger

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  1. Wolfgang Klinger
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Editor information

Editors and Affiliations

  1. Department of Biology, Middle East Technical University, Inönü Bulvari, Ankara, 06531, Turkey

    Emel Arinç

  2. Department of Toxicology, University of Connecticut Health Center, Farmington, Connecticut, 06032, USA

    John B. Schenkman

  3. Department of Toxicology, North Carolina State University, Raleigh, North Carolina, 27695, USA

    Ernest Hodgson

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© 1995 Springer-Verlag Berlin Heidelberg

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Klinger, W. (1995). Drug Metabolism, Lipid Peroxidation and Glutathione. In: Arinç, E., Schenkman, J.B., Hodgson, E. (eds) Molecular Aspects of Oxidative Drug Metabolizing Enzymes. NATO ASI Series, vol 90. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79528-2_25

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  • DOI: https://doi.org/10.1007/978-3-642-79528-2_25

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79530-5

  • Online ISBN: 978-3-642-79528-2

  • eBook Packages: Springer Book Archive

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