Biological Basis of Detoxication

1st Edition - May 28, 1983
Editor: John Caldwell
Language: English
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 1 5 0 1 0 - 1

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.… Read more

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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.

Contributors

Preface

1. Metabolic Formation of Toxic Metabolites

I. Introduction

II. General Examples of Metabolic Activation

III. Specific Examples of Metabolic Activation

IV. Comments

References

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

References

3.Ontogenesis

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

References

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

References

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

References

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

References

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

References

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

References

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

References

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

References

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

References

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

References

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

References

14. Intraindividual and Interindividual Variations

I. Introduction

II. Sources of Intraindividual Variability

III. Sources of Interindividual Variability

References

Index