RT Journal Article
T1 Modeling drug-induced liver injury: current status and future prospects.
A1 Di Zeo-Sánchez, Daniel E
A1 Segovia-Zafra, Antonio
A1 Matilla-Cabello, Gonzalo
A1 Pinazo-Bandera, José M
A1 Andrade, Raúl J
A1 Lucena, M Isabel
A1 Villanueva-Paz, Marina
K1 DILI
K1 Hepatotoxicity
K1 iDILI
K1 immune response
K1 mechanisms
K1 mitochondrial damage
K1 oxidative stress
K1 preclinical model
K1 prediction
AB Idiosyncratic drug-induced liver injury (iDILI) is a challenging and unpredictable multifactorial condition. At present, validated preclinical models for the prediction of the hepatotoxic potential of a given drug are scarce. This review intends to sum up the current knowledge about in vitro (including hepatocyte 2D cultures, cocultures with non-parenchymal cells, 3D configurations and non-typical closer to reality in vitro models), in vivo (covering models for immunological and oxidative stress features, humanized mouse-based and non-rodent models) and in silico approaches for iDILI modeling, highlighting the recent advances in each topic. The future strategy for iDILI modeling should be patient-centered. Future animal and cell-based models, with more predictive value, will be easier to design by using a more translational approach based on mechanisms demonstrated in humans. Genetic and epigenetic information gathered from iDILI patients, together with data from in vitro and in vivo studies, could be used to develop sophisticated predictive in silico models to find compounds with iDILI potential. Collecting genetic, metabolic, and biomarker data from patient cohorts might be another option to create a 'fingerprint' characteristic of people at risk, allowing for the development of new, mechanistic strategies to enhance iDILI in vitro evaluation.
YR 2022
FD 2022-09-16
LK http://hdl.handle.net/10668/19691
UL http://hdl.handle.net/10668/19691
LA en
DS RISalud
RD Apr 9, 2025