Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants

Developed as a one-stop reference source for drug safety and toxicology professionals, this book explains why mitochondrial failure is a crucial step in drug toxicity and how it can be avoided. •    Covers both basic science and applied technology / methods •    Allows readers to understand the basis of mitochondrial function, the preclinical assessments used, and what they reveal about drug effects •    Contains both in vitro and in vivo methods for analysis, including practical screening approaches for drug discovery and development •    Adds coverage about mitochondrial toxicity underlying organ injury, clinical reports on drug classes, and discussion of environmental toxicants affecting mitochondria

Table of Contents:
Volume 1 List of Contributors xvii Foreword xxix Part 1 Basic Concepts 1 1 Contributions of Plasma Protein Binding and Membrane Transporters to Drug?]Induced Mitochondrial Toxicity 3 Gavin P. McStay 2 The Role of Transporters in Drug Accumulation and Mitochondrial Toxicity 15 Kathleen M. Giacomini and Huan?]Chieh Chien 3 Structure–Activity Modeling of Mitochondrial Dysfunction 25 Steve Enoch, Claire Mellor, and Mark Nelms 4 Mitochondria?]Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic Induced Toxicity 35 Haider Raza, F. Peter Guengerich, and Narayan G. Avadhani Part 2 Organ Drug Toxicity: Mitochondrial Etiology 47 5 Mitochondrial Dysfunction in Drug?]Induced Liver Injury 49 Annie Borgne?]Sanchez and Bernard Fromenty 6 Evaluating Mitotoxicity as Either a Single or Multi?]Mechanistic Insult in the Context of Hepatotoxicity 73 Amy L. Ball, Laleh Kamalian, Carol E. Jolly, and Amy E. Chadwick 7 Cardiotoxicity of Drugs: Role of Mitochondria 93 Zoltan V. Varga and Pal Pacher 8 Skeletal Muscle Mitochondrial Toxicity 111 Eric K. Herbert, Saul R. Herbert, and Karl E. Herbert 9 Manifestations of Drug Toxicity on Mitochondria in the Nervous System 133 Jochen H. M. Prehn and Irene Llorente?]Folch 10 Nephrotoxicity: Increasing Evidence for a Key Role of Mitochondrial Injury and Dysfunction and Therapeutic Implications 169 Ana Belén Sanz, Maria Dolores Sanchez?]Niño, Adrian M. Ramos, and Alberto Ortiz 11 Mammalian Sperm Mitochondrial Function as Affected by Environmental Toxicants, Substances of Abuse, and Other Chemical Compounds 185 Sandra Amaral, Renata S. Tavares, Sara Escada?]Rebelo, Andreia F. Silva, and João Ramalho?]Santos Part 3 Methods to Detect Mitochondrial Toxicity: In Vitro, Ex Vivo, In Vivo, Using Cells, Animal Tissues, and Alternative Models 205 12 Biological and Computational Techniques to Identify Mitochondrial Toxicants 207 Robert B. Cameron, Craig C. Beeson, and Rick G. Schnellmann 13 The Parallel Testing of Isolated Rat Liver and Kidney Mitochondria Reveals a Calcium?]Dependent Sensitivity to Diclofenac and Ibuprofen 217 Sabine Schulz, Sabine Borchard, Tamara Rieder, Carola Eberhagen, Bastian Popper, Josef Lichtmannegger, Sabine Schmitt, and Hans Zischka 14 In Vitro Methodologies to Investigate Drug?]Induced Toxicities 229 Rui F. Simões, Teresa Cunha?]Oliveira, Cláudio F. Costa, Vilma A. Sardão, and Paulo J. Oliveira 15 Combined Automated Measurement of Respiratory Chain Complexes and Oxidative Stress: A First Step to an Integrated View of Cell Bioenergetics 249 Marc Conti, Thierry Delvienne, and Sylvain Loric 16 Measurement of Mitochondrial Toxicity by Flow Cytometry 265 Padma Kumar Narayanan and Nianyu Li 17 MitoChip: A Transcriptomics Tool for Elucidation of Mechanisms of Mitochondrial Toxicity 275 Varsha G. Desai, and G. Ronald Jenkins 18 Using 3D Microtissues for Identifying Mitochondrial Liabilities 295 Simon Messner, Olivier Frey, Katrin Rössger, Andy Neilson, and Jens M. Kelm 19 Toward Mitochondrial Medicine: Challenges in Rodent Modeling of Human Mitochondrial Dysfunction 305 David A. Dunn, Michael H. Irwin, Walter H. Moos, Kosta Steliou, and Carl A. Pinkert 20 Measurement of Oxygen Metabolism In Vivo 315 M. P. J. van Diemen, R. Ubbink, F. M. Münker, E. G. Mik, and G. J. Groeneveld 21 Detection of Mitochondrial Toxicity Using Zebrafish 323 Sherine S. L. Chan and Tucker Williamson 22 MiRNA as Biomarkers of Mitochondrial Toxicity 347 Terry R. Van Vleet and Prathap Kumar Mahalingaiah 23 Biomarkers of Mitochondrial Injury After Acetaminophen Overdose: Glutamate Dehydrogenase and Beyond 373 Benjamin L. Woolbright and Hartmut Jaeschke 24 Acylcarnitines as Translational Biomarkers of Mitochondrial Dysfunction 383 Richard D. Beger, Sudeepa Bhattacharyya, Pritmohinder S. Gill, and Laura P. James 25 Mitochondrial DNA as a Potential Translational Biomarker of Mitochondrial Dysfunction in Drug?]Induced Toxicity Studies 395 Afshan N. Malik 26 Predicting Off?]Target Effects of Therapeutic Antiviral Ribonucleosides: Inhibition of Mitochondrial RNA Transcription 407 Jamie J. Arnold and Craig E. Cameron 27 Imaging of Mitochondrial Toxicity in the Kidney 419 Andrew M. Hall, Joana R. Martins, and Claus D. Schuh 28 Imaging Mitochondrial Membrane Potential and Inner Membrane Permeability 429 Anna?]Liisa Nieminen, Venkat K. Ramshesh, and John J. Lemasters 29 Quantifying Skeletal Muscle Mitochondrial Function In Vivo by 31P Magnetic Resonance Spectroscopy 443 Graham J. Kemp   Volume 2 List of Contributors xiii Foreword xxv Part 4 Reports from the Clinic 457 30 Statin and Fibrate?]Induced Dichotomy of Mitochondrial Function 459 Viruna Neergheen, Alex Dyson, Luke Wainwright, and Iain P. Hargreaves 31 Friend or Foe: Can Mitochondrial Toxins Lead to Similar Benefits as Exercise? 475 Sofia Annis, Adeel Safdar, Eduardo Biala, Ayesha Saleem, Housaiyin Li, Priya Gandhi, Zoe Fleischmann, Carmen Castaneda?]Sceppa, Jonathan L. Tilly, Dori C. Woods, and Konstantin Khrapko 32 Involvement of Mitochondrial Dysfunction on the Toxic Effects Caused by Drugs of Abuse and Addiction 487 Daniel José Barbosa, João Paulo Capela, Maria de Lourdes Bastos, and Félix Carvalho 33 Drug?]Induced Mitochondrial Toxicity during Pregnancy 509 Diana Luz Juárez-Flores, Ana Sandra Hernández, Laura Garcia, Mariona Guitart?]Mampel, Marc Catalan?]Garcia, Ingrid Gonzalez?]Casacuberta, Jose César Milisenda, Josep Maria Grau, Francesc Cardellach, Constanza Morén, and Glòria Garrabou 34 Mitochondrial Toxicity in Children and Adolescents Exposed to Antiretroviral Therapy 521 Antoni Noguera?]Julian, Eneritz Velasco?]Arnaiz, and Clàudia Fortuny 35 Drug?]Induced Mitochondrial Cardiomyopathy and Cardiovascular Risks in Children 529 Neha Bansal, Mariana Gerschenson, Tracie L. Miller, Stephen E. Sallan, Jason Czachor, Hiedy Razoky, Ashley Hill, Miriam Mestre, and Steven E. Lipshultz 36 Role of Mitochondrial Dysfunction in Linezolid?]Induced Lactic Acidosis 547 Alessandro Santini, Dario Ronchi, Daniela Piga, and Alessandro Protti 37 Metformin and Lactic Acidosis 559 Jean?]Daniel Lalau 38 Lessons Learned from a Phase I Clinical Trial of Mitochondrial Complex I Inhibition 563 Cecilia C. Low Wang, Jeffrey L. Galinkin, and William R. Hiatt 39 Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies 569 Whitney S. Gibbs, Natalie E. Scholpa, Craig C. Beeson, and Rick G. Schnellmann 40 Mitochondrial Toxicity Induced by Chemotherapeutic Drugs 593 Luciana L. Ferreira, Ana Raquel Coelho, Paulo J. Oliveira, and Teresa Cunha?]Oliveira Part 5 Environmental Toxicants and Mitochondria 613 41 The Mitochondrial Exposome 615 Douglas I. Walker, Kurt D. Pennell, and Dean P. Jones 42 Central Mitochondrial Signaling Mechanisms in Response to Environmental Agents: Integrated Omics for Visualization 639 Young?]Mi Go, Karan Uppal, and Dean P. Jones 43 Detection of Mitochondrial Toxicity of Environmental Pollutants Using Caenorhabditis elegans 655 Laura L. Maurer, Anthony L. Luz, and Joel N. Meyer 44 Persistent Organic Pollutants, Mitochondrial Dysfunction, and Metabolic Syndrome 691 Hong Kyu Lee and Youngmi Kim Pak 45 Cigarette Smoke and Mitochondrial Damage 709 Jalal Pourahmad, Marjan Aghvami, Mohammad Hadi Zarei, and Parvaneh Naserzadeh Index 727

About the Author :
Yvonne Will, PhD, is a Senior Director and the Head of Science and Technology Strategy, Drug Safety Research and Development at Pfizer, Connecticut, USA. In addition to the prior edition of this book, she co-edited Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers(Wiley, 2016). James A. Dykens, PhD, oversees EyeCyte Therapeutics, a start-up developing treatments for progressive blinding diseases via targeting mitochondrial dysfunction. He co-edited the first edition of this book.