Drug-Induced Mitochondrial Dysfunction

Copyright © 2008 John Wiley & Sons, Inc.

Drug-Induced Mitochondrial Dysfunction

Editor(s): James A. Dykens, Yvonne Will

Published Online: 22 JAN 2008

Print ISBN: 9780470111314

Online ISBN: 9780470372531

DOI: 10.1002/9780470372531

About this Book

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About The Product

This is the definitive, one-stop resource on preclinical drug evaluation for potential mitochondrial toxicity, addressing the issue upfront in the drug development process. It discusses mitochondrial impairment to organs, skeletal muscle, and nervous systems and details methodologies used to assess mitochondria function. It covers both in vitro and in vivo methods for analysis and includes the latest models. This is the authoritative reference on drug-induced mitochondrial dysfunction for safety assessment professionals in the pharmaceutical industry and for pharmacologists and toxicologists in both drug and environmental health sciences.

Table of contents

    1. You have free access to this content
      Frontmatter (pages i–xvii)

    1. You have free access to this content
      Color Plates (pages c1–c12)

  3. Part I: Basic Concepts

    1. Chapter 1

      Basic Mitochondrial Physiology in Cell Viability and Death (pages 1–35)

      Lech Wojtczak and Krzysztof Zabłocki

    2. Chapter 2

      Basic Molecular Biology of Mitochondrial Replication (pages 37–70)

      Immo E. Scheffler

    3. Chapter 3

      Drug-Associated Mitochondrial Toxicity (pages 71–126)

      Rhea Mehta, Katie Chan, Owen Lee, Shahrzad Tafazoli and Peter J. O'Brien

    4. Chapter 4

      Pharmacogenetics of Mitochondrial Drug Toxicity (pages 127–139)

      Neil Howell and Corinna Howell

  4. Part II: Organ Drug Toxicity: Mitochondrlal Etiology

    1. Chapter 5

      Features and Mechanisms of Drug-Induced Liver Injury (pages 141–202)

      Dominique Pessayre, Alain Berson and Bernard Fromenty

    2. Chapter 6

      Cardiovascular Toxicity of Mitochondrial Origin (pages 203–234)

      Paulo J. Oliveira, Vilma A. Sardão and Kendall B. Wallace

    3. Chapter 7

      Skeletal Muscle and Mitochondrial Toxicity (pages 235–249)

      Timothy E. Johnson

    4. Chapter 8

      Manifestations of Drug Toxicity on Mitochondria in the Nervous System (pages 251–271)

      Ian J. Reynolds

    5. Chapter 9

      Lipoatrophy and Other Manifestations of Antiretroviral Therapeutics (pages 273–290)

      Ulrich A. Walker

    6. Chapter 10

      Nephrotoxicity (pages 291–310)

      Alberto Ortiz, Alberto Tejedor and Carlos Caramelo

    7. Chapter 11

      Drug Effects in Patients with Mitochondrial Diseases (pages 311–324)

      Eric A. Schon, Michio Hirano and Salvatore Dimauro

  5. Part III: Assessment of Mitochondrial Function in Vitro and in Vivo

    1. Chapter 12

      Polarographic Oxygen Sensors, the Oxygraph, and High-Resolution Respirometry to Assess Mitochondrial Function (pages 325–352)

      Erich Gnaiger

    2. Chapter 13

      Use of Oxygen-Sensitive Fluorescent Probes for the Assessment of Mitochondrial Function (pages 353–371)

      James Hynes, Tom´s C. O'Riordan and Dmitri B. Papkovsky

    3. Chapter 14

      Mitochondrial Dysfunction Assessed Quantitatively in Real Time by Measuring the Extracellular Flux of Oxygen and Protons (pages 373–382)

      David Ferrick, Min Wu, Amy Swift and Andy Neilson

    4. Chapter 15

      Assessment of Mitochondrial Respiratory Complex Function in Vitro and in Vivo (pages 383–395)

      Mark A. Birch-Machin

    5. Chapter 16

      OXPHOS Complex Activity Assays and Dipstick Immunoassays for Assessment of OXPHOS Protein Levels (pages 397–412)

      Sashi Nadanaciva

    6. Chapter 17

      Use of Fluorescent Reporters to Measure Mitochondrial Membrane Potential and the Mitochondrial Permeability Transition (pages 413–431)

      Anna-Liisa Nieminen, Venkat K. Ramshesh and John J. Lemasters

    7. Chapter 18

      Compartmentation of Redox Signaling and Control: Discrimination of Oxidative Stress in Mitochondria, Cytoplasm, Nuclei, and Endoplasmic Reticulum (pages 433–461)

      Patrick J. Halvey, Jason M. Hansen, Lawrence H. Lash and Dean P. Jones

    8. Chapter 19

      Assessing Mitochondrial Protein Synthesis in Drug Toxicity Screening (pages 463–472)

      Edward E. McKee

    9. Chapter 20

      Mitochondrial Toxicity of Antiviral Drugs: A Challenge to Accurate Diagnosis (pages 473–491)

      Michel P. de Baar and Anthony de Ronde

    10. Chapter 21

      Clinical Assessment of Mitochondrial Function via [13C]Methionine Exhalation (pages 493–506)

      Laura Milazzo

    11. Chapter 22

      Assessment of Mitochondrial Dysfunction by Microscopy (pages 507–538)

      Ingrid Pruimboom-Brees, Germaine Boucher, Amy Jakowski and Jeanne Wolfgang

    12. Chapter 23

      Development of Animal Models of Drug-Induced Mitochondrial Toxicity (pages 539–554)

      Urs A. Boelsterli and Yie Hou Lee

    13. Chapter 24

      Noninvasive Assessment of Mitochondrial Function Using Nuclear Magnetic Resonance Spectroscopy (pages 555–574)

      Robert W. Wiseman and J. A. L. Jeneson

    14. Chapter 25

      Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations (pages 575–587)

      Michael P. Murphy

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      Index (pages 589–616)

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