Toxic Interactions

Toxic Interactions

1st Edition - July 28, 1990

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  • Editors: Robin S. Goldstein, William R. Hewitt, Jerry B. Hook
  • eBook ISBN: 9781483269702

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Toxic Interactions is a collection of papers that discusses the basic principles behind the mechanism of toxicological interactions. This book deals with interacting chemicals and their effects on certain exposed organs or molecules. Concerning discussion of the principles, contributed papers explain the role of xenobiotic biotransformation processes in inactivating reactive intermediates of toxicants. Other authors discuss the effects of endogenous molecules and the consequences of chemically induced depletion of protective agents, as well as the pharmacokinetic principles that affect chemical interactions. Several authors also review experiments on the types of chemicals that produce or increase the degree of toxicity. The text reviews the results of liver and kidney injuries from exposure to two or more chemicals, while other papers focus on lung and heart toxicity. For example, direct mechanism of cardio toxicity includes toxicity due to an increase in plasma concentrations of the compound, or as in latent cardiac toxicity that is a product of another action on another system of organs. Professors in pharmacology, practitioners of general medicine, specialists or researchers dealing with microchemistry, toxicology or drug therapy will find this reference valuable.

Table of Contents

  • Contributors


    Part I Principles

    1. Factors to Consider in the Design and Evaluation of Chemical Interaction Studies in Laboratory Animals

    I. Introduction

    II. Theoretical Considerations

    III. Dose-Response Considerations

    IV. Endpoint Considerations

    V. Time-Interval Considerations

    VI. Biotransformation Considerations

    VII. Concluding Remarks


    2. The Role of the Mixed-Function Oxidase System in the Toxication and Detoxication of Chemicals: Relationship to Chemical Interactions

    I. Introduction

    II. Characteristics of the Mixed-Function Oxidase System

    III. Relationship of the Mixed-Function Oxidase System to Chemical Interactions

    IV. Summary


    3. Oxidation of Xenobiotics by Prostaglandin H Synthase

    I. Introduction

    II. Prostaglandin H Synthase

    III. Involvement of Peroxidatic Enzymes in Toxic and Carcinogenic Processes

    IV Mechanism of Prostaglandin H Synthase Metabolism of Xenobiotics

    V Modifying and Preventing Toxic and Carcinogenic Reactions Mediated by Peroxidases

    VI. Summary


    4. The Role of Glutathione in Protection against Chemically Induced Cell Injury

    I. Introduction

    II. Glutathione: Physiological and Biochemical Aspects

    III. Normal Cellular Functions of Glutathione

    IV. Chemically Induced Perturbations in Cellular Glutathione Status

    V. Glutathione and Cell Death

    VI. Conclusion


    5. Displacement Interactions Resulting from Competition for Binding Sites on Proteins

    I. Introduction

    II. General Discussion of Sites of Interactions

    III. Serum Proteins as Sites for Toxic Interactions

    IV. Methods of Experimental Analysis

    V. Analysis of Binding

    VI. Competition

    VII. Prospects for the Future

    VIII. Significance in Medicine and Toxicology


    6. The Impact of Renal Dysfunction on Drug Handling and How to Compensate for It

    I. Introduction

    II. Effects of Renal Dysfunction on Handling of Drugs

    III. Effects of Renal Dysfunction on Response to Drugs

    IV Impact of Renal Dysfunction on Drug-Drug Interactions

    V Strategies for Dose Adjustment in Renal Dysfunction

    VI. Conclusion


    Part II Chemical Interactions and Hepatotoxicity

    7. Use of Microfluorometric and Micropolarographic Techniques to Study Zone-Specific Hepatotoxicity

    I. Introduction

    II. Development of Techniques to Study Functional Aspects of Metabolic Zonation

    III. Characterization of Mixed-Function Oxidation in Periportal and Pericentral Regions

    IV. Conjugation in Periportal and Pericentral Regions

    V. Metabolism of Alcohols in Periportal and Pericentral Regions of the Liver Lobule

    VI. Future Directions


    8. Chemical Alterations of Volatile, Anesthetic Agent-Induced Hepato- and Nephrotoxicity

    I. Introduction

    II. Metabolism of Anesthetic Agents and Toxicological Consequences

    III. Chemical Alterations of Anesthetic Agent-Induced Hepatoand Nephrotoxicity


    9. Prevention of Chemically Induced Liver Injury

    I. Introduction

    II. Inhibition of Metabolic Activation to Reactive Metabolites

    III. Chemical Trapping of Necrogenic Reactive Metabolites

    IV. Increased Intensity of Inactivating Biotransformations

    V. Inhibition of Lipid Peroxidation

    VI. Modulation of Late Stages of the Process


    Part III Alteration of Chemically Induced Nephrotoxicity

    10. Biochemical Mechanisms of Chemically Induced Nephrotoxicity

    I. Introduction

    II. General Aspects of Renal Damage Produced by Toxic Chemicals

    III. Biotransformation of Toxic Chemicals in the Kidney

    IV. Mechanisms Responsible for Chemically Induced Nephrotoxicity

    V. Potentiation of the Action of Nephrotoxicants by Environmental Contaminants

    VI. Conclusion


    11. Toxic Actions of the Aminoglycoside Antibiotics on the Kidney

    I. Introduction

    II. Pathogenesis

    III. Molecular Determinants of Aminoglycoside Toxicity

    IV. Clinical Features of Aminoglycoside Nephrotoxicity

    V. Interactions with Other Drugs


    12. Ketonic Potentiation of Haloalkane-Induced Nephrotoxicity

    I. Introduction

    II. Ketonic Solvent Potentiation of CHC13 Nephrotoxicity

    III. Interactions between 2-Hexanone and Other Nephrotoxicants

    IV. Mechanisms Involved in 2-Hexanone Potentiation of Nephrotoxicity

    V. Conclusions


    13. Chronic Chemical Injury to the Kidney

    I. Introduction

    II. Chronic Chemical Nephropathies Recognized in Humans

    III. Chronic Chemical Nephrotoxicity in Experimental Systems

    IV. Conclusions


    Part IV Chemical Interactions and Other Target Organ Toxicities

    14. Toxicological Interactions in the Pathogenesis of Lung Injury

    I. Toxicological Interactions and Human Lung Disease

    II. Mechanisms of Toxicological Interaction in the Lung

    III. Conclusions


    15. Drug-Induced Cardiotoxicity

    I. Introduction

    II. Regulation of Calcium Transport in Cardiac Muscle

    III. Role of Calcium in the Cardiotoxic Actions of Drugs

    IV. Interactions of Cardiotoxic Drugs



Product details

  • No. of pages: 502
  • Language: English
  • Copyright: © Academic Press 1990
  • Published: July 28, 1990
  • Imprint: Academic Press
  • eBook ISBN: 9781483269702

About the Editors

Robin S. Goldstein

William R. Hewitt

Jerry B. Hook

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