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Effects of thrombopoietin on the protection against doxorubicin-induced cardiotoxicity.

To Man Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 85-105). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / (in Chinese) --- p.iv / Acknowledgements --- p.vi / Publications --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xii / List of Figures --- p.xiii / List of Abbreviations --- p.xiv / Chapter CHAPTER 1: --- General Introduction --- p.1 / Chapter Section 1.1 --- Background and Clinical Application of Anthracylines --- p.1 / Chapter Section 1.2 --- DOX-induced Cardiotoxicity --- p.3 / Chapter 1.2.1 --- Types of Cardiotoxicity --- p.4 / Chapter 1.2.1.1 --- Acute Cardiotoxicity --- p.4 / Chapter 1.2.1.2 --- Chronic Cardiotoxicity --- p.5 / Chapter 1.2.2 --- Subcellular Effects of DOX --- p.6 / Chapter 1.2.2.1 --- Ultrastructural Lesions --- p.6 / Chapter 1.2.2.2 --- Effects on Mitochondrial Functions --- p.7 / Chapter 1.2.2.3 --- Effects on Sarcoplasmic reticulum (SR) Functions --- p.8 / Chapter Section 1.3 --- Mechanisms of DOX-induced Cardiotoxicity --- p.8 / Chapter 1.3.1 --- Formation of Free Radicals --- p.9 / Chapter 1.3.1.1 --- Generation of Free Radicals by DOX --- p.10 / Chapter 1.3.1.2 --- Cardiac damage by Free radicals --- p.12 / Chapter 1.3.2 --- Induction of Apoptosis --- p.14 / Chapter 1.3.2.1 --- Characteristics and Pathway of Apoptosis --- p.14 / Chapter 1.3.2.2 --- Mitochondria and Apoptosis --- p.15 / Chapter 1.3.2.3 --- Caspases and Apoptosis --- p.17 / Chapter 1.3.2.4 --- Apoptosis and DOX-induced Cardiotoxicity --- p.18 / Chapter Section 1.4 --- Strategies to Reduce DOX-induced Cardiotoxicity --- p.19 / Chapter 1.4.1 --- Dosage optimization and Schedule modification --- p.19 / Chapter 1.4.2 --- Anthracycline Analogues --- p.21 / Chapter 1.4.3 --- Cardioprotective Agents --- p.21 / Chapter Section 1.5 --- Thrombopoietin --- p.23 / Chapter CHAPTER 2: --- Hypotheses and Objectives --- p.30 / Chapter CHAPTER 3: --- Methodology --- p.33 / Chapter Section 3.1 --- Methods --- p.33 / Chapter 3.1.1 --- Culture of Rat H9C2 Myoblast Cell Line and Primary Neonatal Rat Cardiomyocytes --- p.33 / Chapter 3.1.1.1 --- Maintenance of Cell Line --- p.33 / Chapter 3.1.1.2 --- Culture of Primary Neonatal Rat Cardiomyocytes --- p.34 / Chapter 3.1.2 --- Effects of Thrombopoietin on Cell Viability of Rat H9C2 Myoblast Cell Line and Beating Rates of Primary Rat Cardiomyocytes --- p.35 / Chapter 3.1.2.1 --- Cell Viability assay --- p.35 / Chapter 3.1.2.2 --- Beating Rate of Primary Beating Cardiomyocytes --- p.36 / Chapter 3.1.3 --- Effects of Thrombopoietin on the Protection against DOX-induced Heart Injury In Vivo --- p.36 / Chapter 3.1.3.1 --- Animals --- p.36 / Chapter 3.1.3.2 --- Experimental Protocol --- p.37 / Chapter 3.1.3.3 --- Echocardiography --- p.38 / Chapter 3.1.3.4 --- Blood Cell Counts --- p.39 / Chapter 3.1.3.5 --- Histopathology --- p.39 / Chapter 3.1.4 --- Effects of Thrombopoietin on Apoptosis and Mitochondrial Integrity of Rat H9C2 Myoblast Cell Line and Apoptosis In Vivo --- p.40 / Chapter 3.1.4.1 --- Determination of Externalized Phosphatidylserine --- p.40 / Chapter 3.1.4.2 --- Determination of Active Caspase-3 Expression --- p.41 / Chapter 3.1.4.3 --- Assessment of Mitochondrial Integrity --- p.42 / Chapter 3.1.4.4 --- TUNEL assay --- p.43 / Chapter 3.1.5 --- Statistical Analysis --- p.44 / Chapter CHAPTER 4: --- Effects of Thrombopoietin on Cell Viability of Rat H9C2 Myoblast Cell Line and Beating Rates of Primary Neonatal Rat Cardiomyocytes --- p.46 / Chapter Section 4.1 --- Results --- p.46 / Chapter 4.1.1 --- Effects of TPO on DOX-induced Cell Death --- p.46 / Chapter 4.1.2 --- Effects of TPO on the Beating Rates of Primary Cardiomyocytes --- p.47 / Chapter Section 4.2 --- Discussion --- p.47 / Chapter CHAPTER 5: --- Effects of Thrombopoietin on the Protection Against DOX-induced Heart Injury In Vivo --- p.54 / Chapter Section 5.1 --- Results --- p.54 / Chapter 5.1.1 --- General Observations and Survival --- p.54 / Chapter 5.1.2 --- Blood Cell Counts --- p.55 / Chapter 5.1.3 --- Cardiac Functions by Echocardiography --- p.56 / Chapter 5.1.4 --- Gross Anatomic Changes and Pathology of the Myocardium --- p.57 / Chapter Section 5.2 --- Discussion --- p.58 / Chapter CHAPTER 6: --- Effects of Thrombopoietin on Apoptosis and Mitochondrial Integrity of H9C2 Cell Line and Apoptosis In Vico --- p.69 / Chapter Section 6.1 --- Results --- p.69 / Chapter 6.1.1 --- Determination of Externalized Phosphatidylserine --- p.69 / Chapter 6.1.2 --- Determination of Active Caspase-3 Activity --- p.70 / Chapter 6.1.3 --- Assessment of Mitochondrial Membrane Potential --- p.70 / Chapter 6.1.4 --- Determination of Apoptosis by TUNEL assay --- p.72 / Chapter Section 6.2 --- Discussion --- p.72 / Chapter CHAPTER 7: --- General Discussion and Conclusion --- p.83 / References --- p.85

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_325638
Date January 2006
ContributorsTo, Man Yin., Chinese University of Hong Kong Graduate School. Division of Medical Sciences.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xv, 105 leaves : ill. (some col.) ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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