Toxic Interactions

ContributorsPreface 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 ReferencesPart 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 ReferencesPart 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.