Toxic Interactions - 1st Edition - ISBN: 9780122895159, 9781483269702

Toxic Interactions

1st Edition

Editors: Robin S. Goldstein William R. Hewitt Jerry B. Hook
eBook ISBN: 9781483269702
Imprint: Academic Press
Published Date: 28th July 1990
Page Count: 502
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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



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




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© Academic Press 1990
Academic Press
eBook ISBN:

About the Editor

Robin S. Goldstein

William R. Hewitt

Jerry B. Hook

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