RT Journal Article
T1 Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network
A1 Segovia-Zafra, Antonio
A1 Villanueva-Paz, Marina
A1 Serras, Ana Sofía
A1 Matilla-Cabello, Gonzalo
A1 Bodoque-García, Ana
A1 Di Zeo-Sánchez, Daniel Enrique
A1 Niu, Hao
A1 Álvarez-Álvarez, Ismael
A1 Sanz-Villanueva, Laura
A1 Godec, Sergej
A1 Milisav, Irina
A1 Bagnaninchi, Pierre
A1 Andrade, Raúl J.
A1 Lucena, M. Isabel
A1 Fernandez-Checa, J.C.
A1 Cubero, Francisco Javier
A1 Paiva Miranda, Joana
A1 Nelson, Leonard J.
K1 Hígado - Enfermedades
K1 Farmacología
K1 Toxicidad - Ensayos in vitro
K1 Medicamentos - Ensayos
AB Background & AimsIdiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112).MethodsFollowing 2020 PRISMA guidelines, original research articles focusing on DILI which used in vitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified ‘Toxicological Data Reliability Assessment Tool’.ResultsA total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations.ConclusionsExtensive analysis highlighted the lack of agreement on control compounds for in vitro DILI assessment. Following comprehensive in vitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of in vitro models of DILI is proposed.
PB Elsevier
YR 2024
FD 2024
LK https://hdl.handle.net/10630/32783
UL https://hdl.handle.net/10630/32783
LA eng
NO Antonio Segovia-Zafra, Marina Villanueva-Paz, Ana Sofia Serras, Gonzalo Matilla-Cabello, Ana Bodoque-García, Daniel E. Di Zeo-Sánchez, Hao Niu, Ismael Álvarez-Álvarez, Laura Sanz-Villanueva, Sergej Godec, Irina Milisav, Pierre Bagnaninchi, Raúl J. Andrade, M Isabel Lucena, José C. Fernández-Checa, Francisco Javier Cubero, Joana Paiva Miranda, Leonard J. Nelson, Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network, Journal of Hepatology, Volume 81, Issue 4, 2024, Pages 630-640, ISSN 0168-8278, https://doi.org/10.1016/j.jhep.2024.04.026
NO Funding for open access charge: Universidad de Málaga / CBUA.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026