University of Groningen
Exploring anti-fibrotic drugs Luangmonkong, Theerut
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Publication date: 2017
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Luangmonkong, T. (2017). Exploring anti-fibrotic drugs: Focusing on an ex vivo model of fibrosis. University of Groningen.
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Paranymphs
Dorenda Oosterhuis Su Suriguga
The research presented in this PhD thesis was performed at the Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, the Netherlands.
Cover and layout: Theerut Luangmonkong
Printed: Proefschriftmaken
ISBN (printed version): 978-94-034-0187-4 ISBN (electronic version): 978-94-034-0186-7
©Theerut Luangmonkong, 2017
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Exploring anti-fibrotic drugs
Focusing on an ex vivo model of fibrosis
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus Prof. E. Sterken
and in accordance with
the decision by the College of Deans. This thesis will be defended in public on Monday 27 November 2017 at 09.00 hours
by
Theerut Luangmonkong
born on 9 October 1982 in Bangkok, Thailand
Supervisors Prof. dr. P. Olinga Prof. dr. C. Suthisisang Co-supervisor Dr. H.A.M. Mutsaers Assessment Committee
Prof. dr. R.A. Bank Prof. dr. K.N. Faber
Prof. dr. M. Kruithof - de Julio Prof. dr. K. Sripha
Contents
Introduction, scope and aims 7
Part A: Exploring anti-fibrotic drugs for the treatment of liver fibrosis 9
Chapter A1 Evaluating the anti-fibrotic potency of galunisertib in a human ex vivo model of liver fibrosis 11
Chapter A2 In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF- 33
Chapter A3 Human precision-cut liver slices as a model to test anti-fibrotic drugs in the early onset of liver fibrosis 49 Chapter A4 Targeting oxidative stress for the treatment of liver fibrosis 69
Part B: Development of novel disease models 89
Chapter B1 Pathophysiological model of non-alcoholic fatty liver disease using precision-cut liver slices 91
Chapter B2 Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis 103
General discussion and perspectives 117
Summary – Samenvatting – สรุป 129
Acknowledgements 135
Lists of supplementary box
Box I Transforming growth factors 10 Box II Small molecule drugs 32 Box III Free radicals 68 Box IV Metabolic syndrome 90
