Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants

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 Belen Sanz, Maria Dolores Sanchez?]Nino, 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 Joao 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. Simoes, Teresa Cunha?]Oliveira, Claudio F. Costa, Vilma A. Sardao, 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 Roessger, 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. Muenker, 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 Jose Barbosa, Joao Paulo Capela, Maria de Lourdes Bastos, and Felix Carvalho

33 Drug?]Induced Mitochondrial Toxicity during Pregnancy 509
Diana Luz Juarez-Flores, Ana Sandra Hernandez, Laura Garcia, Mariona Guitart?]Mampel, Marc Catalan?]Garcia, Ingrid Gonzalez?]Casacuberta, Jose Cesar Milisenda, Josep Maria Grau, Francesc Cardellach, Constanza Moren, and Gloria Garrabou

34 Mitochondrial Toxicity in Children and Adolescents Exposed to Antiretroviral Therapy 521
Antoni Noguera?]Julian, Eneritz Velasco?]Arnaiz, and Claudia 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

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• Toxicologia médica

mitochondrial dysfunction, mitochondrial toxicity, mitochondrial medicine, mitochondrial pharmacology, drug safety, drug transport and detoxification, drug-mitochondria interactions