Drug-Induced Mitochondrial Dysfunction

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.Content: Chapter 1 Basic Mitochondrial Physiology in Cell Viability and Death (pages 1–35): Lech Wojtczak and Krzysztof ZablockiChapter 2 Basic Molecular Biology of Mitochondrial Replication (pages 37–70): Immo E. SchefflerChapter 3 Drug?Associated Mitochondrial Toxicity (pages 71–126): Rhea Mehta, Katie Chan, Owen Lee, Shahrzad Tafazoli and Peter J. O'BrienChapter 4 Pharmacogenetics of Mitochondrial Drug Toxicity (pages 127–139): Neil Howell and Corinna HowellChapter 5 Features and Mechanisms of Drug?Induced Liver Injury (pages 141–202): Dominique Pessayre, Alain Berson and Bernard FromentyChapter 6 Cardiovascular Toxicity of Mitochondrial Origin (pages 203–234): Paulo J. Oliveira, Vilma A. Sardao and Kendall B. WallaceChapter 7 Skeletal Muscle and Mitochondrial Toxicity (pages 235–249): Timothy E. JohnsonChapter 8 Manifestations of Drug Toxicity on Mitochondria in the Nervous System (pages 251–271): Ian J. ReynoldsChapter 9 Lipoatrophy and Other Manifestations of Antiretroviral Therapeutics (pages 273–290): Ulrich A. WalkerChapter 10 Nephrotoxicity (pages 291–310): Alberto Ortiz, Alberto Tejedor and Carlos CarameloChapter 11 Drug Effects in Patients with Mitochondrial Diseases (pages 311–324): Eric A. Schon, Michio Hirano and Salvatore DimauroChapter 12 Polarographic Oxygen Sensors, the Oxygraph, and High?Resolution Respirometry to Assess Mitochondrial Function (pages 325–352): Erich GnaigerChapter 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. PapkovskyChapter 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 NeilsonChapter 15 Assessment of Mitochondrial Respiratory Complex Function in Vitro and in Vivo (pages 383–395): Mark A. Birch?MachinChapter 16 OXPHOS Complex Activity Assays and Dipstick Immunoassays for Assessment of OXPHOS Protein Levels (pages 397–412): Sashi NadanacivaChapter 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. LemastersChapter 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. JonesChapter 19 Assessing Mitochondrial Protein Synthesis in Drug Toxicity Screening (pages 463–472): Edward E. McKeeChapter 20 Mitochondrial Toxicity of Antiviral Drugs: A Challenge to Accurate Diagnosis (pages 473–491): Michel P. de Baar and Anthony de RondeChapter 21 Clinical Assessment of Mitochondrial Function via [13C]Methionine Exhalation (pages 493–506): Laura MilazzoChapter 22 Assessment of Mitochondrial Dysfunction by Microscopy (pages 507–538): Ingrid Pruimboom?Brees, Germaine Boucher, Amy Jakowski and Jeanne WolfgangChapter 23 Development of Animal Models of Drug?Induced Mitochondrial Toxicity (pages 539–554): Urs A. Boelsterli and Yie Hou LeeChapter 24 Noninvasive Assessment of Mitochondrial Function Using Nuclear Magnetic Resonance Spectroscopy (pages 555–574): Robert W. Wiseman and J. A. L. JenesonChapter 25 Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations (pages 575–587): Michael P. Murphy