Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants

  • ID: 4342860
  • Book
  • 816 Pages
  • John Wiley and Sons Ltd
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A major public health concern, despite regulatory vigilance, is untoward toxicity and other pharmaceutical side effects. This toxicity is often idiosyncratic, and usually not discovered until after a large population has been exposed and injured. Recent laboratory evaluations show that many of these drugs impact mitochondrial function. The realization that mitochondrial toxicity is a widespread and important issue in drug toxicity is increasingly appreciated, and most pharmaceutical companies now either have the technology to assess this risk themselves, or do so via contract research organizations.

Developed as a one–stop reference source for drug safety and toxicology professionals, the  second edition of Drug and Environmental Induced Mitochondrial Dysfunction explains why mitochondrial failure is a crucial step in drug toxicity and how it can be avoided. It allows readers to understand the basis of mitochondrial function and the preclinical assessments used and what they reveal about drug effects. The focus is on how the requisite technology continues to evolve and the recent emergence of clinical techniques capable of detecting drug–induced mitochondrial toxicity in patients.

Added coverage in the 2nd edition includes how and why mitochondrial toxicity underlies organ injury, clinical reports on drug classes, and discussion of environmental toxicants that can affect mitochondria. With chapters contributed by leading specialists in their areas, Drug and Environmental Induced Mitochondrial Dysfunction, 2nd Edition continues to serve as a valuable resource for safety assessment professionals in the pharmaceutical industry including bench scientists and managers and for pharmacologists and toxicologists in both drug and environmental health sciences.Drug and Environmental Induced Mitochondrial Dysfunction provides ample reminders of the intimate connections between mitochondria, pharmacology, and toxicology.  The book takes a rather systematic approach to mitochondrial pharmacology and toxicology and, for this reason, will be of use to even those outside of strict drug discovery.

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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 3Gavin P. McStay

2 The Role of Transporters in Drug Accumulation and Mitochondrial Toxicity 15Kathleen M. Giacomini and Huan ]Chieh Chien

3 Structure Activity Modeling of Mitochondrial Dysfunction 25Steve Enoch, Claire Mellor, and Mark Nelms

4 Mitochondria ]Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic Induced Toxicity 35Haider Raza, F. Peter Guengerich, and Narayan G. Avadhani

Part 2 Organ Drug Toxicity: Mitochondrial Etiology 47

5 Mitochondrial Dysfunction in Drug ]Induced Liver Injury 49Annie Borgne ]Sanchez and Bernard Fromenty

6 Evaluating Mitotoxicity as Either a Single or Multi ]Mechanistic Insult in the Context of Hepatotoxicity 73Amy L. Ball, Laleh Kamalian, Carol E. Jolly, and Amy E. Chadwick

7 Cardiotoxicity of Drugs: Role of Mitochondria 93Zoltan V. Varga and Pal Pacher

8 Skeletal Muscle Mitochondrial Toxicity 111Eric K. Herbert, Saul R. Herbert, and Karl E. Herbert

9 Manifestations of Drug Toxicity on Mitochondria in the Nervous System 133Jochen H. M. Prehn and Irene Llorente ]Folch

10 Nephrotoxicity: Increasing Evidence for a Key Role of Mitochondrial Injury and Dysfunction and Therapeutic Implications 169Ana 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 185Sandra 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 207Robert 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 217Sabine 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 229Rui 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 249Marc Conti, Thierry Delvienne, and Sylvain Loric

16 Measurement of Mitochondrial Toxicity by Flow Cytometry 265Padma Kumar Narayanan and Nianyu Li

17 MitoChip: A Transcriptomics Tool for Elucidation of Mechanisms of Mitochondrial Toxicity 275Varsha G. Desai, and G. Ronald Jenkins

18 Using 3D Microtissues for Identifying Mitochondrial Liabilities 295Simon Messner, Olivier Frey, Katrin Rössger, Andy Neilson, and Jens M. Kelm

19 Toward Mitochondrial Medicine: Challenges in Rodent Modeling of Human Mitochondrial Dysfunction 305David A. Dunn, Michael H. Irwin, Walter H. Moos, Kosta Steliou, and Carl A. Pinkert

20 Measurement of Oxygen Metabolism In Vivo 315M. P. J. van Diemen, R. Ubbink, F. M. Münker, E. G. Mik, and G. J. Groeneveld

21 Detection of Mitochondrial Toxicity Using Zebrafish 323Sherine S. L. Chan and Tucker Williamson

22 MiRNA as Biomarkers of Mitochondrial Toxicity 347Terry R. Van Vleet and Prathap Kumar Mahalingaiah

23 Biomarkers of Mitochondrial Injury After Acetaminophen Overdose: Glutamate Dehydrogenase and Beyond 373Benjamin L. Woolbright and Hartmut Jaeschke

24 Acylcarnitines as Translational Biomarkers of Mitochondrial Dysfunction 383Richard 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 395Afshan N. Malik

26 Predicting Off ]Target Effects of Therapeutic Antiviral Ribonucleosides: Inhibition of Mitochondrial RNA Transcription 407Jamie J. Arnold and Craig E. Cameron

27 Imaging of Mitochondrial Toxicity in the Kidney 419Andrew M. Hall, Joana R. Martins, and Claus D. Schuh

28 Imaging Mitochondrial Membrane Potential and Inner Membrane Permeability 429Anna ]Liisa Nieminen, Venkat K. Ramshesh, and John J. Lemasters

29 Quantifying Skeletal Muscle Mitochondrial Function In Vivo by 31P Magnetic Resonance Spectroscopy 443Graham 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 459Viruna Neergheen, Alex Dyson, Luke Wainwright, and Iain P. Hargreaves

31 Friend or Foe: Can Mitochondrial Toxins Lead to Similar Benefits as Exercise? 475Sofia 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 487Daniel José Barbosa, João Paulo Capela, Maria de Lourdes Bastos, and Félix Carvalho

33 Drug ]Induced Mitochondrial Toxicity during Pregnancy 509Diana 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 521Antoni Noguera ]Julian, Eneritz Velasco ]Arnaiz, and Clàudia Fortuny

35 Drug ]Induced Mitochondrial Cardiomyopathy and Cardiovascular Risks in Children 529Neha 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 547Alessandro Santini, Dario Ronchi, Daniela Piga, and Alessandro Protti

37 Metformin and Lactic Acidosis 559Jean ]Daniel Lalau

38 Lessons Learned from a Phase I Clinical Trial of Mitochondrial Complex I Inhibition 563Cecilia C. Low Wang, Jeffrey L. Galinkin, and William R. Hiatt

39 Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies 569Whitney S. Gibbs, Natalie E. Scholpa, Craig C. Beeson, and Rick G. Schnellmann

40 Mitochondrial Toxicity Induced by Chemotherapeutic Drugs 593Luciana L. Ferreira, Ana Raquel Coelho, Paulo J. Oliveira, and Teresa Cunha ]Oliveira

Part 5 Environmental Toxicants and Mitochondria 613

41 The Mitochondrial Exposome 615Douglas I. Walker, Kurt D. Pennell, and Dean P. Jones

42 Central Mitochondrial Signaling Mechanisms in Response to Environmental Agents: Integrated Omics for Visualization 639Young ]Mi Go, Karan Uppal, and Dean P. Jones

43 Detection of Mitochondrial Toxicity of Environmental Pollutants Using Caenorhabditis elegans 655Laura L. Maurer, Anthony L. Luz, and Joel N. Meyer

44 Persistent Organic Pollutants, Mitochondrial Dysfunction, and Metabolic Syndrome 691Hong Kyu Lee and Youngmi Kim Pak

45 Cigarette Smoke and Mitochondrial Damage 709Jalal Pourahmad, Marjan Aghvami, Mohammad Hadi Zarei, and Parvaneh Naserzadeh

Index 727

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