Mechanistic Toxicology: The Molecular Basis of How Chemicals Disrupt Biological Targets, Second Edition, 2nd Edition (Paperback) book cover

Mechanistic Toxicology

The Molecular Basis of How Chemicals Disrupt Biological Targets, Second Edition, 2nd Edition

By Urs A. Boelsterli

CRC Press

416 pages | 210 B/W Illus.

Purchasing Options:$ = USD
Paperback: 9780849372728
pub: 2007-03-23
$87.95
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Hardback: 9781138473621
pub: 2017-08-25
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Description

A thorough understanding of cellular and molecular mechanisms involved in the individual expression of toxic effects provides an important tool for assessment of human health risk. New aspects, major advances, and new areas in molecular and cellular biology and toxicology demand updated sources of information to elucidate the functional mechanics of human toxicology.

Mechanistic Toxicology: The Molecular Basis of How Chemicals Disrupt Biological Targets, Second Edition retains the accessible format of the original to present the general principles that link xenobiotic-induced toxicity with the molecular pathways that underlie these toxic effects. Extensively illustrated, this book forms a conceptual bridge between multiple events at the molecular level and the determinants of toxicity at the physiological and cellular level. Specific examples of drugs, environmental pollutants, and other chemicals are carefully chosen to illustrate and highlight the fundamental mechanisms of toxicity at different toxicokinetic and toxicodynamic levels. The book includes references and review articles at the end of each chapter, as well as boxed text for relevant review information on biological, biochemical, molecular, and toxicological background. Linking molecular pathways to more general biomedical contexts, the author ensures that the reader is not lost in the details and instead receives a broad understanding of the processes underlying xenobiotic toxicity.

New in the Second Edition

  • Updated chapters
  • Types of toxic responses
  • Disruption of signal transduction by xenobiotics
  • Disruption of mitochondrial function
  • Novel mechanisms derived from systems toxicology
  • Reviews

    'Students taking formal training in toxicology would definitely benefit from adding this book to their collection, since it covers many recent advances in the field.' - British Toxicology Society Newsletter

    'This recently-published volume is a clear state-of-the-art explanation and description of how chemicals disrupt biological targets on a molecular basis. It is a beauty!'. - Toxicology Letters

    Table of Contents

    Introduction

    Why Molecular Mechanisms?

    Toxicokinetics and Toxicodynamics

    Types of Toxic Responses

    Adaptation to Cellular Stress

    Toxic Responses

    Disruption of Cytoprotective Mechanisms

    Organ-Selective Toxicity

    Biological Basis of Organ-Selective Toxicity

    Selective Hepatotoxicity and Nephrotoxicity

    Cellular Transport and Selective Accumulation of Potentially Toxic Xenobiotics

    Transmembrane Transport of Xenobiotics

    Cell-Specific Delivery of Xenobiotics to Intracellular Targets by Physiological Uptake Systems

    Xenobiotic Export Pumps

    Bioactivation of Xenobiotics to Reactive Metabolites

    Biotransformation and Bioactivation/-Inactivation

    Phase I (Functionalization) and Phase II (Conjugation) Reactions

    Net Balance of Bioactivation/Bioinactivation for Risk Assessment

    Mechanisms of Phototoxicity

    Protective Mechanisms Against Reactive Metabolites: The Stress Response

    Xenobiotic-Induced Oxidative Stress: Cell Injury, Signaling, and Gene Regulation

    Reactive Oxygen Species (ROS) and Oxidoreductive Stress

    Toxicological Consequences of Oxidative Stress

    Interference with Antioxidant Defense Mechanisms

    Intracellular Signaling and Gene Regulation by Oxidative Stress

    Disruption of Cellular Calcium Homeostasis

    Xenobiotic-Induced Alterations in Intracellular Ca2+ Distribution

    Toxicological Consequences of Increased Cytosolic Ca2+ Concentrations

    Mechanisms of Necrotic and Apoptotic Cell Death

    Necrosis

    Apoptosis

    Impairment of Cell Proliferation and Tissue Repair

    The Cell Cycle

    Stimulation of DNA Synthesis and Cell Proliferation: Xenobiotics as Mitogens

    Inhibition of Cell Proliferation by Xenobiotics

    Inhibition of Tissue Repair

    Covalent Binding of Reactive Metabolites to Cellular Macromolecules

    Electrophiles and Nucleophilic Targets

    Covalent Protein Binding

    Covalent DNA Binding

    Immune Mechanisms

    Xenobiotic-Induced Activation of the Innate Immune System

    Immunosuppression by Xenobiotics

    Immune-Mediated Toxicity

    Cytokine-Mediated Toxicity

    Tumor Necrosis Factor-a and Other Proinflammatory Cytokines

    Chemokines and Inflammatory Cell Recruitment

    Specific Inactivation of Enzymes and Other Proteins

    Inactivation of Thiol-Containing Enzymes

    Disruption of Acetylcholinesterase Activity

    Transthyretin Binding and Inactivation: Disruption of Thyroid Function

    Inactivation of DNA-mismatch-repair Proteins

    Interactions of Xenobiotics with Ion Transporters

    Interactions with Neuronal Na+ Channels

    Interactions with the Na+/K+ Pump

    Selective Inhibition of Cardiac Myocyte K+ Channels and QT Prolongation

    Nuclear Receptor-Mediated Toxicity

    The Aryl Hydrocarbon Receptor (AHR)

    Xenoestrogens and Antiandrogens

    Peroxisome Proliferator-Activated Receptors (PPARs)

    Retinoic Acid Receptor (RAR)

    Activation or Disruption of Cellular Signal Transduction by Xenobiotics

    Signaling: Sensing and Responding

    Interference with Signal Transduction by Xenobiotics

    Disruption of Mitochondrial Function and Mitochondria-Mediated Toxicity

    Mitochondrial Targets and Xenobiotic-Induced Bioenergy Crisis

    Protonophoretic and Uncoupling Activity of Xenobiotics

    Inhibition of NADH Production

    Inhibition of the Electron Transport Chain and Increased Generation of ROS

    Mitochondrial Membrane Permeabilization

    Selective Depletion of Mitochondrial DNA

    Novel Mechanisms Derived from Systems Toxicology

    Index

    Subject Categories

    BISAC Subject Codes/Headings:
    MED096000
    MEDICAL / Toxicology
    SCI026000
    SCIENCE / Environmental Science
    SCI049000
    SCIENCE / Life Sciences / Biology / Molecular Biology