Dykens / Will Drug-Induced Mitochondrial Dysfunction

1. Auflage 2008
ISBN: 978-0-470-37252-4
Verlag: John Wiley & Sons
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 652 Seiten, E-Book

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.

Autoren/Hrsg.

Dykens, James A.

Will, Yvonne

Inhaltsverzeichnis

Contributors.
Preface.
Part I: Basic Concepts.
1. Basic Mitochondrial Physiology in Cell Viability and Death(Lech Wojtczak and Krzysztof Zabtocki).
2. Basic Molecular Biology of Mitochondrial Replication (Immo E.Scheffler).
3. Drug-Associated Mitochondrial Toxicity (Rhea Mehta, KatieChan, Owen Lee, Shahrzad Tafazoli, and Peter J. O'Brien).
4. Pharmacogenetics of Mitochondrial Drug Toxicity (Neil Howelland Corinna Howell).
Part II: Organ Drug Toxicity: Mitochondrial Etiology.
5. Features and Mechanisms of Drug-Induced Liver Injury(Dominique Pessayre, Alain Berson, and Bernard Fromenty).
6. Cardiovascular Toxicity of Mitochondrial Origin (Paulo J.Oliveira, Vilma A. Saradao, and Kendall B. Wallace).
7. Skeletal Muscle and Mitochondrial toxicity (Timothy E.Johnson).
8. Manifestations of Drug Toxicity on Mitochondria in theNervous System (Ian J. Reynolds).
9. Lipoatrophy and Other Manifestations of AntiretroviralTherapeutics (Ulrich A. Walker).
10. Nephrotoxocity (Alberto Ortiz, Alberto Tejedor, and CarlosCaramelo).
11. Drug Effects in Patients with Mitochondrial Diseases (EricA. Schon, Michio Hirano, and Salvatore DiMauro).
Part III: Assessment of Mitochondrial Function in Vitro andIn Vivo.
12. Polarographic Oxygen Sensors, the Oxygraph, andHigh-Resolution Respirometry to Assess Mitochondrial Function(Erich Gnaiger).
13. Use of Oxygen-Sensitive Fluorescent Probes for the Assesmentof Mitochondrial Function (James Hynes, Tomas C. O'riordan, andDmitri B. Papkovsky).
14. Mitochondrial Dysfunction Assessed Quantitatively in RealTime by Measuring the Extracellular Flux of Oxygen and Protons(David Ferrick, Min Wu, Amy Swift, and Andy Neilson).
15. Assessment of Mitochondrial Respiratory Complex Function InVitro and In Vivo (Mark A. Birch -Machin).
16. OXPHOS Complex Activity Assays and Dipstick Immunoassays forAssessment of OXPHOS Protein Levels (Sashi Nadanaciva).
17. Use of Fluorescent Reporters to Measure MitochondrialMembrane Potential and the Mitochondrial Permeability Transition(Anna Liisa Nieminen, Benkat K. Ramshesh, and John L.Lemasters).
18. Compartmentation of Redox Signaling and Control:Discrimination of Oxidative Stress in Mitochondria, Cytoplasm,Nuclei, and endoplasmic Reticulum (Patrick J. Halvey, Jason M.Hansen, Lawrence H. Lash, and Dean P. Hones).
19. Assessing Mitochondrial Protein Synthesis in Drug ToxicityScreening (Edward E. McKee).
20. Mitochondrial Toxicity of Antiviral Drugs: A Challenge toAccurate Diagnosis (Michel P. de Baar and Anthony de Ronde).
21. Clinical Assessment of Mitochondrial Function via[¯13C]Methionine Exhalation (Laura Milazzo).
22. Assessment of Mitochondrial Dysfunction by Microscopy(Ingrid Pruimboom-Brees, Germaine Boucher, Amy Jakowski, and JeanneWolfgang).
23. Development of Animal Models of Drug-Induced MitochondrialToxicity (Urs A. Boelsterli and Yie Hou Lee).
24. Noninvasive Assessment of Mitochondrial Function UsingNuclear Magnetic Resonance Spectroscopy (Robert W. Wiseman and J.A.L. Jeneson).
25. Targeting Antioxidants to Mitochondria by Conjugation toLipophilic Cations (Michael P. Murphy).
Index.

Über Autor(innen)

James A. Dykens, PhD, is an Associate Research Fellow inPfizer's Drug Safety Research and Development Department. Currentlyin Sandwich, England, he previously worked in a similar role withPfizer in La Jolla, California. Prior to his work with Pfizer, Dr.Dykens was the senior director of technology development forMIGENIX Inc., a senior scientist and the director of businessdevelopment at MitoKor, Inc., and a senior principal scientist atParke-Davis Pharmaceutical Research. Dr. Dykens has publishedextensively on drug-induced mitochondrial dysfunction, on the roleof mitochondrial free radical production in the etiology ofneurodegenerative diseases, and on the physiological ecology ofmarine symbioses.
Yvonne Will, PhD, works in Pfizer's Exploratory SafetyDifferentiation Group in Groton, Connecticut. Prior to thisposition, she led Pfizer's Investigative Biochemical Toxicity Groupwithin the Drug Safety Research and Development Department in LaJolla. Before joining Pfizer, Dr. Will worked on mitochondrialproteomics and physiology at MitoKor, Inc. Dr. Will has authored ahost of articles and book chapters. She is a member of the Societyof Toxicology and a frequent speaker for groups like ACT and WorldPharmaceutical Congress.