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.
