2026-05-28T16:48:12Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/235062026-02-03T11:21:39Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Villanueva-Paz, Marina
author
Morán, Laura
author
López-Alcántara, Nuria
author
Freixo, Cristiana
author
Andrade-Bellido, Raúl Jesús
author
Lucena-González, María Isabel
author
Cubero, Francisco Javier
2021-12-21T13:14:20Z
2021-12-21T13:14:20Z
2021-03-05
Villanueva-Paz,M.;Morán, L.; López-Alcántara, N.; Freixo, C.; Andrade, R.J.; Lucena, MI.; Cubero, F.J. Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice. Antioxidants 2021, 10, 390. https://doi.org/10.3390/antiox10030390
https://hdl.handle.net/10630/23506
10.3390/antiox10030390
Idiosyncratic drug-induced liver injury (DILI) is a type of hepatic injury caused by an uncommon drug adverse reaction that can develop to conditions spanning from asymptomatic liver laboratoryabnormalitiestoacuteliverfailure(ALF)anddeath.Thecellularandmolecularmecha- nisms involved in DILI are poorly understood. Hepatocyte damage can be caused by the metabolic activation of chemically active intermediate metabolites that covalently bind to macromolecules (e.g., proteins, DNA), forming protein adducts—neoantigens—that lead to the generation of oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, which can eventually lead to cell death. In parallel, damage-associated molecular patterns (DAMPs) stimulate the immune response, whereby inflammasomes play a pivotal role, and neoantigen presentation on specific human leukocyte antigen (HLA) molecules trigger the adaptive immune response. A wide array of antioxidant mechanisms exists to counterbalance the effect of oxidants, including glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), which are pivotal in detoxification. These get compromised during DILI, triggering an imbalance between oxidants and antioxidants defense systems, generating oxidative stress. As a result of exacerbated oxidative stress, several danger signals, including mitochondrial damage, cell death, and inflammatory markers, and microRNAs (miRNAs) related to extracellular vesicles (EVs) have already been reported as mechanis- tic biomarkers. Here, the status quo and the future directions in DILI are thoroughly discussed, with a special focus on the role of oxidative stress and the development of new biomarkers.
eng
Estrés oxidativo
Marcadores bioquímicos
Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice
journal article
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2021. Oxidative Stress in Drug-Induced Liver Injury (DILI) From Mechanisms to Biomarkers for Use in Clinical Practice.pdf