Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction
| Autor: | Zeus Pérez-Valdés, Daniel E. Di Zeo-Sánchez, Eduardo García-Fuentes, Marina Villanueva-Paz, Raúl J. Andrade, M. Isabel Lucena, Carlos López-Gómez, Antonio Segovia-Zafra |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Mitochondrial damage Hígado Drug-induced liver injury business.industry media_common.quotation_subject Patología mitocondrial Estrés oxidativo Preclinical models Review RM1-950 Bioinformatics Personalized medicine Inmunorrespuesta Drug development Oxidative stress Mechanisms Medicine Therapeutics. Pharmacology General Pharmacology Toxicology and Pharmaceutics Immune response business media_common |
| Zdroj: | RIUMA. Repositorio Institucional de la Universidad de Málaga instname Acta Pharmaceutica Sinica B, Vol 11, Iss 12, Pp 3685-3726 (2021) Acta Pharmaceutica Sinica. B |
| Popis: | 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. Graphical abstract This review highlights the most recent idiosyncratic drug-induced liver injury (iDILI) experimental models and future perspectives in iDILI modelling, focusing mainly on the cellular, animal and in silico approaches.Image 1 |
| Databáze: | OpenAIRE |
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