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.

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. 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 ReferencesPart 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 ReferencesIndex