RT Journal Article
T1 Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction
A1 Segovia-Zafra, Antonio
A1 Di Zeo-Sánchez, Daniel E.
A1 López-Gómez, Carlos
A1 Pérez-Valdés, Zeus
A1 García-Fuentes, Eduardo
A1 Andrade, Raúl 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 Enfermedad hepática inducida por sustancias y drogas
K1 Estrés oxidativo
K1 Inmunidad
K1 Medicina de precisión
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.
PB Elsevier BV
YR 2021
FD 2021
LK http://hdl.handle.net/10668/4120
UL http://hdl.handle.net/10668/4120
LA en
NO Segovia-Zafra A, Di Zeo-Sánchez DE, López-Gómez C, Pérez-Valdés Z, García-Fuentes E, Andrade RJ, et al. Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction. Acta Pharm Sin B. 2021 Dec;11(12):3685-3726
DS RISalud
RD Apr 11, 2025