Advanced preclinical models for evaluation of drug-induced liver injury - consensus statement by the European Drug-Induced Liver Injury Network [PRO-EURO-DILI-NET].

Autor: Fernandez-Checa JC; Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Científicas (CSIC), Spain; Liver Unit, Hospital Clínic, Barcelona, Spain; Instituto Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain; USC Research Center for ALPD, Keck School of Medicine, Los Angeles, United States, CA 90033. Electronic address: checa229@yahoo.com., Bagnaninchi P; Center for Regenerative Medicine, Institute for Regenerative and Repair, The University of Edinburgh, Edinburgh, UK, EH16 4UU; School of Engineering, Institute for Bioengineering, The University of Edinburgh, Faraday Building, Colin Maclaurin Road, EH9 3 DW, Scotland, UK., Ye H; Department of Immunology, Ophthalmology & ENT, Complutense University School of Medicine, 28040 Madrid, Spain; Health Research Institute Gregorio Marañón (IiSGM), 28007 Madrid, Spain., Sancho-Bru P; Instituto Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain., Falcon-Perez JM; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain; Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, 48160, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Bizkaia, 48015, Spain., Royo F; Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, 48160, Spain., Garcia-Ruiz C; Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Científicas (CSIC), Spain; Liver Unit, Hospital Clínic, Barcelona, Spain; Instituto Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain; USC Research Center for ALPD, Keck School of Medicine, Los Angeles, United States, CA 90033., Konu O; Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara, Turkey; Interdisciplinary Neuroscience Program, Bilkent University, Ankara, Turkey; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey., Miranda J; Research Institute for iMedicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal., Lunov O; Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, Prague, Czech Republic., Dejneka A; Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, Prague, Czech Republic., Elfick A; Institute for Bioengineering, School of Engineering, The University of Edinburgh, Edinburgh EH8 3DW, UK., McDonald A; Institute for Bioengineering, School of Engineering, The University of Edinburgh, Edinburgh EH8 3DW, UK., Sullivan GJ; University of Oslo and the Oslo University Hospital, Oslo, Norway; Hybrid Technology Hub-Center of Excellence, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Pediatric Research, Oslo University Hosptial, Oslo, Norway., Aithal GP; National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and University of Nottingham, Nottingham, UK., Lucena MI; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain; Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, UICEC SCReN, Universidad de Málaga, Málaga, Spain., Andrade RJ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain; Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación, Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Malaga, Spain., Fromenty B; INSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, France., Kranendonk M; Center for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, Universidade NOVA de Lisboa, Lisbon, Portugal., Cubero FJ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 28029, Spain; Department of Immunology, Ophthalmology & ENT, Complutense University School of Medicine, 28040 Madrid, Spain; Health Research Institute Gregorio Marañón (IiSGM), 28007 Madrid, Spain., Nelson LJ; Center for Regenerative Medicine, Institute for Regenerative and Repair, The University of Edinburgh, Edinburgh, UK, EH16 4UU; School of Engineering, Institute for Bioengineering, The University of Edinburgh, Faraday Building, Colin Maclaurin Road, EH9 3 DW, Scotland, UK; Institute of Biological Chemistry, Biophysics and Bioengineering (IB3), School of Engineering and Physical Sciences (EPS), Heriot-Watt University, Edinburgh EH12 2AS, Scotland, UK. Electronic address: l.nelson@ed.ac.uk.
Jazyk: angličtina
Zdroj: Journal of hepatology [J Hepatol] 2021 Oct; Vol. 75 (4), pp. 935-959. Date of Electronic Publication: 2021 Jun 24.
DOI: 10.1016/j.jhep.2021.06.021
Abstrakt: Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF) and one of the leading indications for liver transplantation in Western societies. Given the wide use of both prescribed and over the counter drugs, DILI has become a major health issue for which there is a pressing need to find novel and effective therapies. Although significant progress has been made in understanding the molecular mechanisms underlying DILI, our incomplete knowledge of its pathogenesis and inability to predict DILI is largely due to both discordance between human and animal DILI in preclinical drug development and a lack of models that faithfully recapitulate complex pathophysiological features of human DILI. This is exemplified by the hepatotoxicity of acetaminophen (APAP) overdose, a major cause of ALF because of its extensive worldwide use as an analgesic. Despite intensive efforts utilising current animal and in vitro models, the mechanisms involved in the hepatotoxicity of APAP are still not fully understood. In this expert Consensus Statement, which is endorsed by the European Drug-Induced Liver Injury Network, we aim to facilitate and outline clinically impactful discoveries by detailing the requirements for more realistic human-based systems to assess hepatotoxicity and guide future drug safety testing. We present novel insights and discuss major players in APAP pathophysiology, and describe emerging in vitro and in vivo pre-clinical models, as well as advanced imaging and in silico technologies, which may improve prediction of clinical outcomes of DILI.
Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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