RT Generic
T1 Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction
A1 Segovia-Zafra, Antonio
A1 Zeo-Sanchez, Daniel E. Di
A1 Lopez-Gomez, Carlos
A1 Perez-Valdes, Zeus
A1 Garcia-Fuentes, Eduardo
A1 Andrade, Raul J.
A1 Lucena, M. Isabel
A1 Villanueva-Paz, Marina
K1 Drug-induced liver injury
K1 Preclinical models
K1 Mechanisms
K1 Oxidative stress
K1 Mitochondrial damage
K1 Immune response
K1 Personalized medicine
K1 Hepatocyte-like cells
K1 Pluripotent stem-cells
K1 In-silico models
K1 Endoplasmic-reticulum stress
K1 Necrosis-factor-alpha
K1 Gamma-glutamylcysteine synthetase
K1 Induced mitochondrial dysfunction
K1 Lymphocyte-transformation test
K1 Sandwich-cultured hepatocytes
K1 Acid-induced toxicity
AB Idiosyncratic drug-induced liver injury (iDILI) encompasses the unexpected harms that prescription and non-prescription drugs, herbal and dietary supplements can cause to the liver. iDILI remains a major public health problem and a major cause of drug attrition. Given the lack of biomarkers for iDILI prediction, diagnosis and prognosis, searching new models to predict and study mechanisms of iDILI is necessary. One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI. Thus, major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients. However, there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms. Therefore, there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development. Here, the current experimental models and the future directions in iDILI modelling are thoroughly discussed, focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models. We also comment about in silico approaches and the increasing relevance of patient-derived cellular models. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
PB Inst materia medica, chinese acad medical sciences
SN 2211-3835
YR 2021
FD 2021-12-01
LK https://hdl.handle.net/10668/26940
UL https://hdl.handle.net/10668/26940
LA en
DS RISalud
RD Apr 10, 2025