2026-08-29T12:40:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/182792024-11-28T14:46:40Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16938col_20.500.12105_16927col_20.500.12105_16978
Repisalud
author
Villanueva-Paz, Marina
author
Morán, Laura
author
López-Alcántara, Nuria
author
Freixo, Cristiana
author
Andrade, Raúl J.
author
Lucena, M Isabel
author
Cubero, Francisco Javier
authoraffiliation
[Villanueva-Paz,M; Andrade,RJ; Lucena,MI] Unidad de Gestión Clínica de Gastroenterología, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Málaga, Spain. [Morán,L; López-Alcántara,N; Cubero,FJ] Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain. [Morán,L] Health Research Institute Gregorio Marañón (IiSGM), Madrid, Spain. [Freixo,C] CINTESIS, Center for Health Technology and Services Research, do Porto University School of Medicine, Porto, Portugal. [Cubero,FJ] 12 de Octubre Health Research Institute (imas12), Madrid, Spain.
2024-02-19T15:26:20Z
2024-02-19T15:26:20Z
2021-03-05
10.3390/antiox10030390
2076-3921
Antioxidants
http://hdl.handle.net/10668/3663
33807700
http://hdl.handle.net/20.500.12105/18279
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 laboratory abnormalities to acute liver failure (ALF) and death. The cellular and molecular mechanisms 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 mechanistic 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
DILI
Oxidative stress
Risk factors
Biomarkers
Mechanisms
Estrés oxidativo
Factores de riesgo
Biomarcadores
Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice
review article