Biological Basis of Detoxication

Biological Basis of Detoxication

1st Edition - May 28, 1983

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  • Editor: John Caldwell
  • eBook ISBN: 9780323150101

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Biological Basis of Detoxication focuses on the biological processes involved in detoxication, with emphasis on the biochemistry of the removal of xenobiotics from an organism. Topics range from the formation of toxic metabolites and compounds that are not metabolized at all to the tissue distribution and nutritional considerations, the kinetics and mechanisms of the metabolic and excretory processes, and the integration of xenobiotic metabolism in the activation and detoxication of carcinogens. Organized into 14 chapters, this book begins with an overview of the enzymatic basis for the metabolic activation of foreign compounds in forming reactive chemical intermediates. The first few chapters discuss the identification of reactive electrophiles derived from xenobiotics, intratissue distribution of activating and detoxicating enzymes, enzymatic and non-enzymatic modes of xenobiotic metabolism, and unmetabolized compounds. The middle chapters explore the biological basis of detoxication of oxygen free radicals, physiologic and kinetic aspects of the fate of xenobiotics, excretion of xenobiotics, and effects of nutrition on detoxication. The remaining chapters look at the relationships between the enzymes of detoxication and host defense mechanisms, metabolic basis of target organ toxicity, the enzymatic factor in selective toxicity, and intraindividual and interindividual variations in rates of hepatic metabolism of exogenous chemicals. Pharmacologists, toxicologists, and biochemists will find this book highly informative.

Table of Contents

  • Contributors


    1. Metabolic Formation of Toxic Metabolites

    I. Introduction

    II. General Examples of Metabolic Activation

    III. Specific Examples of Metabolic Activation

    IV. Comments


    2. Integration of Xenobiotic Metabolism in Carcinogen Activation

    and Detoxication

    I. Introduction

    II. Identification of Reactive Electrophiles Derived from Xenobiotics

    III. Cell Specificity of Xenobiotic Effects

    IV. Classification of Xenobiotic Activation Pathways

    V. Partition of Metabolic Pathways

    VI. Regioselectivity and Stereoselectivity of Cytochrome P-450

    VII. Epoxide Hydrolase

    VIII. Absolute Monooxygenase Activity in the Activation Pathway

    IX. Cellular Cosubstrates of Xenobiotic Metabolism

    X. UDPglucuronyltransferases and Sulfotransferases

    XI. Glutathione S-Transferases

    XII. Inhibitors of Cellular Transferase Activity

    XIII. Xenobiotic Metabolism in the Nuclear Envelope

    XIV. Transport of Reactive Intermediates and Precursors

    XV. Comments



    I. Introduction

    II. Developmental Profiles of Drug-Metabolizing Enzymes

    III. Factors Influencing Drug-Metabolizing Enzyme Development

    IV. Comments: The Biological and Clinical Consequences of Drug-Metabolizing Enzyme Ontogenesis


    4.Intratissue Distribution of Activating and Detoxicating Enzymes

    I. Introduction

    II. Distribution within the Liver

    III. Distribution within the Lung

    IV. Distribution within the Skin

    V. Comments


    5.Nonenzymatic Biotransformation

    I. Introduction

    II. Reactions with Macromolecules as Borderline Cases

    III. Reactions with Endogenous Nucleophiles

    IV. Reactions with Endogenous Electrophiles

    V. Breakdown and Rearrangement Reactions of Xenobiotics and Prodrugs in Acidic and Neutral Aqueous Media

    VI. Reactions between Two Xenobiotics

    VII. Comments


    6. Unmetabolized Compounds

    I. Introduction

    II. Criteria for Classification of a Foreign Compound as Being Unmetabolized

    III. Properties of Unmetabolized Compounds

    IV. Toxicological Implications

    V. Comments


    7.Biological Basis of Detoxication of Oxygen Free Radicals

    I. Introduction

    II. Oxygen Free Radicals

    III. Defense Mechanisms: Enzymatic and Nonenzymatic

    IV. Factors Influencing Defense Mechanisms and the Production of Oxygen Free Radicals

    V. Biological Systems Associated with Increased Oxygen Free Radical Production

    VI. Comments


    8. Fate of Xenobiotics: Physiologic and Kinetic Considerations

    I. Introduction

    II. The Xenobiotic

    III. Hemodynamics

    IV. Xenobiotic Metabolism

    V. Xenobiotic Excretion

    VI. Eliminating Organs

    VII. Comments


    9. Excretion Mechanisms

    I. Introduction

    II. Renal Handling of Organic Anions and Cations

    III. Biliary Excretion of Xenobiotics

    IV. Salivary Excretion

    V. Excretion into Milk

    VI. Excretion into Expired Air

    VII. Comments


    10. Impact of Nutrition on Detoxication

    I. Introduction

    II. Fasting/Starvation

    III. Protein

    IV. Carbohydrate

    V. Lipid

    VI. Trace Nutrients—Vitamins and Minerals

    VII. Comments


    11. Relationships between the Enzymes of Detoxication and Host Defense Mechanisms

    I. Introduction

    II. Nonspecific Immunostimulants

    III. Adjuvant-Induced Arthritis

    IV. Reticuloendothelial System

    V. Interferon

    VI. Infection in Animals

    VII. Viral Infection in Humans


    12. Metabolic Basis of Target Organ Toxicity

    I. Introduction

    II. Distribution of the Toxin as a Factor in Target Organ Toxicity

    III. Role of Metabolism in Determining Target Organ Toxicity

    IV. Role of Specific Function of the Tissue

    V. Comments


    13. Enzymes in Selective Toxicity

    I. Introduction

    II. The Toxicological Significance of Enzymatic Conversion

    III. The Enzymatic Factor in Selective Toxicity

    IV. The Enzymatic Factor in Resistance

    V. Comments


    14. Intraindividual and Interindividual Variations

    I. Introduction

    II. Sources of Intraindividual Variability

    III. Sources of Interindividual Variability



Product details

  • No. of pages: 444
  • Language: English
  • Copyright: © Academic Press 1983
  • Published: May 28, 1983
  • Imprint: Academic Press
  • eBook ISBN: 9780323150101

About the Editor

John Caldwell

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