Drug-Induced Mitochondrial Dysfunction

by Editor: James A. Dykens; Editor: Yvonne Will

• ISBN13: 9780470372524
• ISBN10: 0470372524
• Format: eBook
• Copyright: 2008-09-01
• Publisher: Wiley-Interscience

Summary

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.

Table of Contents

Contributors

Preface

Basic Concepts

Basic Mitochondrial Physiology in Cell Viability and Death

Basic Molecular Biology of Mitochondrial Replication

Drug-Associated Mitochondrial Toxicity

Pharmacogenetics of Mitochondrial Drug Toxicity

Organ Drug Toxicity: Mitochondrial Etiology

Features and Mechanisms of Drug-Induced Liver Injury

Cardiovascular Toxicity of Mitochondrial Origin

Skeletal Muscle and Mitochondrial toxicity

Manifestations of Drug Toxicity on Mitochondria in the Nervous System

Lipoatrophy and Other Manifestations of Antiretroviral Therapeutics

Nephrotoxocity

Drug Effects in Patients with Mitochondrial Diseases

Assessment of Mitochondrial Function in Vitro and In Vivo

Polarographic Oxygen Sensors, the Oxygraph, and High-Resolution Respirometry to Assess Mitochondrial Function

Use of Oxygen-Sensitive Fluorescent Probes for the Assesment of Mitochondrial Function

Mitochondrial Dysfunction Assessed Quantitatively in Real Time by Measuring the Extracellular Flux of Oxygen and Protons

Assessment of Mitochondrial Respiratory Complex Function In Vitro and In Vivo

OXPHOS Complex Activity Assays and Dipstick Immunoassays for Assessment of OXPHOS Protein Levels

Use of Fluorescent Reporters to Measure Mitochondrial Membrane Potential and the Mitochondrial Permeability Transition

Compartmentation of Redox Signaling and Control: Discrimination of Oxidative Stress in Mitochondria, Cytoplasm, Nuclei, and endoplasmic Reticulum

Assessing Mitochondrial Protein Synthesis in Drug Toxicity Screening

Mitochondrial Toxicity of Antiviral Drugs: A Challenge to Accurate Diagnosis

Clinical Assessment of Mitochondrial Function via [¹³C]Methionine Exhalation

Assessment of Mitochondrial Dysfunction by Microscopy

Development of Animal Models of Drug-Induced Mitochondrial Toxicity

Noninvasive Assessment of Mitochondrial Function Using Nuclear Magnetic Resonance Spectroscopy

Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations

Index

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