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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\u2014neoantigens\u2014that 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.<\/jats:p>","DOI":"10.3390\/antiox10030390","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:46:09Z","timestamp":1614944769000},"page":"390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":198,"title":["Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4728-201X","authenticated-orcid":false,"given":"Marina","family":"Villanueva-Paz","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Gastroenterolog\u00eda, Servicio de Farmacolog\u00eda Cl\u00ednica, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de M\u00e1laga, CIBERehd, 29071 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, 28040 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n (IiSGM), 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"L\u00f3pez-Alc\u00e1ntara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-6885","authenticated-orcid":false,"given":"Cristiana","family":"Freixo","sequence":"additional","affiliation":[{"name":"CINTESIS, Center for Health Technology and Services Research, do Porto University School of Medicine, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-0757","authenticated-orcid":false,"given":"Ra\u00fal J.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Gastroenterolog\u00eda, Servicio de Farmacolog\u00eda Cl\u00ednica, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de M\u00e1laga, CIBERehd, 29071 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-4896","authenticated-orcid":false,"given":"M Isabel","family":"Lucena","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Gastroenterolog\u00eda, Servicio de Farmacolog\u00eda Cl\u00ednica, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de M\u00e1laga, CIBERehd, 29071 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-650X","authenticated-orcid":false,"given":"Francisco Javier","family":"Cubero","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, 28040 Madrid, Spain"},{"name":"12 de Octubre Health Research Institute (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1124\/jpet.109.162651","article-title":"Intrinsic versus idiosyncratic drug-induced hepatotoxicity\u2014Two villains or one?","volume":"332","author":"Roth","year":"2010","journal-title":"J. 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