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oai:riuma.uma.es:10630/236142026-02-03T11:09:18Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga author Segovia-Zafra, Antonio author Di Zeo-Sánchez, Daniel Enrique author López-Gómez, Carlos author Pérez-Valdés, Zeus author García-Fuentes, Eduardo author Andrade-Bellido, Raúl Jesús author Lucena-González, María Isabel author Villanueva-Paz, Marina 2022-01-14T09:40:57Z 2022-01-14T09:40:57Z 2021-12 Segovia-Zafra A, Di Zeo-Sánchez DE, López-Gómez C, Pérez-Valdés Z, García-Fuentes E, Andrade RJ, Lucena MI, Villanueva-Paz M. Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction. Acta Pharm Sin B. 2021 Dec;11(12):3685-3726. doi: 10.1016/j.apsb.2021.11.013. https://hdl.handle.net/10630/23614 10.1016/j.apsb.2021.11.013 Idiosyncratic drug-induced liver injury (iDILI) encompasses the unexpected harms that pre- scription 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 hu- man 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. eng Patología mitocondrial Hígado Estrés oxidativo Inmunorrespuesta Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction journal article 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 URL https://riuma.uma.es/bitstreams/ef77ff98-eb7a-4a76-9f42-d1b407b0a610/download File MD5 343435105f832054b71af57498b8de4c 2938618 application/pdf Preclinical models of idiosyncratic drug-induced liver injury (iDILI) Moving towards prediction.pdf