Toxic Interactions

Contributors

Preface

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

References


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

References


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

References


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

References


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

References


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

References

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

References


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

References


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

References

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

References


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

References


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

References


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

References

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

References


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

References

Index