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Hepatotoxicity
From Genomics to In Vitro and In Vivo Models

Saura C. Sahu (Edited by), SC Sahu (Author)

9780470057162, Wiley

Hardback, published 14 December 2007

704 pages
25 x 17.5 x 4.4 cm, 1.389 kg

"This provides valuable insight into the current and future directions of research in this field and wil be a valuable resource of up-to-date information for toxicologists, risk assessors, and regulators in academia, industry and government." (Doody's, August 2008)

This book addresses all the current, up-to-date developments in this scientific discipline. Liver is the chief metabolizing site in the body, and thus, it is a major target organ for drug and chemical toxicity. Therefore, hepatotoxicity is an important endpoint in the safety evaluation of drugs and chemicals.

Contributions from leading investigators in hepatotoxicity research address current developments in this scientific discipline and discuss use of current cutting edge technology such as microarrays in hepatotoxicity thus providing a better understanding of hepatotoxins, their interactions and mechanisms of action.

This valuable authoritative source of information is the first book to address this topic for nearly ten years, making it an essential resource for readers from a wide range of disciplines such as toxicology, pharmacology, hepatology, drug toxicity and food science.

Contributors xi

Preface xvii

Acknowledgements xix

Section 1 Models for Hepatotoxicity Testing

1 Current in vitro Models to Study Drug-Induced Liver Injury 3
Julio C. Davila, Jinghai J. Xu, Keith A. Hoffmaster, Peter J. O’Brien and Stephen C. Storm

2 Utilization of an in vitro Hepatotoxicity Test in the Early Stage of Drug Discovery 57
Ikuo Horii, Hiroshi Yamada, Rie Kikkawa, Toshinori Yamamoto, Tamio Fukushima and Kaori Tomizawa

3 Use of Hepatocytes for Characterizing a Candidate Drug’s Metabolism and Drug Interaction Potential 69
Srikanth C. Nallani, John M. Strong and Shiew Mei Huang

4 Human-Based in vitro Experimental Systems for the Evaluation of Human Drug Safety 89
Albert P. li

5 Hepatocytes as a Model for Screening Food-Related Hepatotoxins and Studying Mechanisms of their Toxicity 105
Saura C. Sahu

6 Some Experimental Models of Liver Damage 119
Pablo Muriel

Section 2 Hepatocyte Cultures

7 Application of Short- and Long-Term Hepatocyte Cultures to Predict Toxicities 141
Gregor Tuschl, Jens Hrach, Philip G. Hewitt and Stefan O. Mueller

Section 3 Biomarkers of Hepatotoxicity

8 Biomarkers of Mycotoxin Exposure in Liver Toxicity 177
Angela J. Harris

Section 4 Mechanisms of Hepatotoxicity

9 Mechanisms of Toxic Liver Injury 191
Nora Anderson and Jürgen Borlak

10 A Role of Cytochrome P450 in Quinone-Induced Hepatotoxicity 287
Yasuhiro Ishihara and Norio Shimamoto

11 A Mechanistic View of Troglitazone Hepatotoxicity 299
Rawiwan Maniratanachote and Tsuyoshi Yokoi

12 Role of the Kupffer Cell in Hepatotoxicity and Hepatocarcinogenesis 313
James E. Klaunig, Stacy M. Corthals, Lisa M. Kamendulis and Binu K. Philip

13 Sinusoidal Cells in Liver Injury and Repair 341
Carol R. Gardner and Debra L. Laskin

14 Cytokines in Liver Diseases 371
Pablo Muriel

15 Bile Acids as Modulators of Apoptosis 391
Rui E. Castro, Susana Solá, Clifford J. Steer and Cecília M.P. Rodrigues

16 Drug-Induced Intrahepatic Cholestasis by Interaction with the Hepatic Bile Salt Export Pump (BSEP) 421
Christoph Funk, Johannes Noé, Renée Portmann, Ruben Alvarez-Sánchez, Florian Klammers, Christiane Lamy, Axel Paehler and Michael Pantze

Section 5 Genomics of Hepatotoxicity

17 Application of Toxicogenomics in Predicting Hepatotoxicity – Potentials and Challenges 449
Wen Lin, Guoxiang Shen, Tin Oo Khor and Ah-Ng Tony Kong

18 Genomic Profiling of Liver Injury 465
Kevin Gerrish and David E. Malarkey

19 Use of DNA Arrays in Understanding Hepatic Test Systems 489
Angela J. Harris and Daniel A. Casciano

20 Prediction of Hepatotoxicity Based on the Toxicogenomics Database 507
Tetsuro Urushidani

21 Relationship between N-acetyltransferase-2 Gene Polymorphism and Isoniazid-Induced Hepatotoxicity 531
Yasuo Shimizu, Kunio Dobashi and Masatomo Mori

Section 6 Gender Differences in Hepatotoxicity

22 Human and Animal-Based Differences in Hepatic Xenobiotic Metabolism and Toxicity 539
Peter J. O’Brien, Katie Chan and Raymond J. Poon

Section 7 Hepatotoxicity and Hepatocarcinogenicity

23 Hepatotoxicity in Oncology Drug Development 565
Wei Chen, Kenneth Hastings and John K. Leighton

24 The Potent Rat Hepatocarcinogen Methapyrilene: An Hypothesis Regarding its Hepatotoxicology 577
Daniel A. Casciano

Section 8 Hepatotoxicity and Botanical Supplements

25 Botanical Supplements and Hepatotoxicity 591
Shabana Khan, Ikhlas Khan and Larry Walker

Section 9 Risk Analysis of Hepatotoxins

26 Physiologically Based Pharmokinetic Modeling and Risk Assessment of Hepatotoxicants 609
Kannan Krishnan

Index 635

Subject Areas: Chemistry [PN]

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