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Drug Safety Evaluation

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Cover of 'Drug Safety Evaluation'

Table of Contents

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    Book Overview
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    Chapter 1 Nonclinical Development of Combination Drugs
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    Chapter 2 Juvenile Nonclinical Safety Studies in Support of Pediatric Drug Development
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    Chapter 3 Procedures of Necropsy and Tissue Sampling
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    Chapter 4 Tissue Sampling and Processing for Histopathology Evaluation
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    Chapter 5 Principles and Methods of Immunohistochemistry
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    Chapter 6 Applications of Mass Spectrometry Imaging for Safety Evaluation
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    Chapter 7 In Vivo Rat T-Lymphocyte Pig-a Assay: Detection and Expansion of Cells Deficient in the GPI-Anchored CD48 Surface Marker for Analysis of Mutation in the Endogenous Pig-a Gene
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    Chapter 8 Detection of In Vivo Mutation in the Pig-a Gene of Mouse Bone Marrow Erythroids
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    Chapter 9 The Use of Bacterial Repair Endonucleases in the Comet Assay
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    Chapter 10 Automated Patch-Clamp Methods for the hERG Cardiac Potassium Channel
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    Chapter 11 Impedance Measurement in Induced Pluripotent Stem Cell-Derived Cardiomyocytes
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    Chapter 12 Target Safety Assessment: Strategies and Resources
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    Chapter 13 NMR and MS Methods for Metabolomics
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    Chapter 14 Protocols and Applications of Cellular Metabolomics in Safety Studies Using Precision-Cut Tissue Slices and Carbon 13 NMR
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    Chapter 15 Statistical Analysis of Quantitative RT-PCR Results
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    Chapter 16 Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes
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    Chapter 17 FETAX Assay for Evaluation of Developmental Toxicity
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    Chapter 18 Evaluation of Embryotoxicity Using the Zebrafish Model
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    Chapter 19 Absolute Quantification of Toxicological Biomarkers via Mass Spectrometry
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    Chapter 20 Next-Generation Sequencing to Investigate Urinary microRNAs from Macaca fascicularis (Cynomolgus Monkey)
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    Chapter 21 Quantitative RT-PCR for MicroRNAs in Biofluids
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    Chapter 22 Chromogenic In Situ Hybridization Methods for microRNA Biomarker Monitoring of Drug Safety and Efficacy
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    Chapter 23 Urine Exosome Isolation and Characterization
Attention for Chapter 16: Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes
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Chapter title
Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes
Chapter number 16
Book title
Drug Safety Evaluation
Published in
Methods in molecular biology, January 2017
DOI 10.1007/978-1-4939-7172-5_16
Pubmed ID
Book ISBNs
978-1-4939-7170-1, 978-1-4939-7172-5
Authors

Jean-Pierre Marchandeau, Gilles Labbe

Abstract

Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug. The use of cells instead of isolated mitochondria allows one to test the toxic effect of a parent compound and its metabolites. The use of rat hepatocytes can detect drugs involved in drug-induced liver injuries (DILI). The method consists in measuring oxygen consumption by using a Clark electrode in a chamber containing a suspension of hepatocytes preincubated with drug.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 3 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 3 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 67%
Unknown 1 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 67%
Unknown 1 33%