PMID- 33807700
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230919
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 3
DP  - 2021 Mar 5
TI  - Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to 
      Biomarkers for Use in Clinical Practice.
LID - 10.3390/antiox10030390 [doi]
LID - 390
AB  - 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.
FAU - Villanueva-Paz, Marina
AU  - Villanueva-Paz M
AUID- ORCID: 0000-0003-4728-201X
AD  - Unidad de Gestion Clinica de Gastroenterologia, Servicio de Farmacologia Clinica, 
      Instituto de Investigacion Biomedica de Malaga-IBIMA, Hospital Universitario 
      Virgen de la Victoria, Universidad de Malaga, CIBERehd, 29071 Malaga, Spain.
FAU - Moran, Laura
AU  - Moran L
AD  - Department of Immunology, Ophthalmology and ENT, Complutense University School of 
      Medicine, 28040 Madrid, Spain.
AD  - Health Research Institute Gregorio Maranon (IiSGM), 28009 Madrid, Spain.
FAU - Lopez-Alcantara, Nuria
AU  - Lopez-Alcantara N
AD  - Department of Immunology, Ophthalmology and ENT, Complutense University School of 
      Medicine, 28040 Madrid, Spain.
FAU - Freixo, Cristiana
AU  - Freixo C
AUID- ORCID: 0000-0001-5028-6885
AD  - CINTESIS, Center for Health Technology and Services Research, do Porto University 
      School of Medicine, 4200-319 Porto, Portugal.
FAU - Andrade, Raul J
AU  - Andrade RJ
AUID- ORCID: 0000-0002-1565-0757
AD  - Unidad de Gestion Clinica de Gastroenterologia, Servicio de Farmacologia Clinica, 
      Instituto de Investigacion Biomedica de Malaga-IBIMA, Hospital Universitario 
      Virgen de la Victoria, Universidad de Malaga, CIBERehd, 29071 Malaga, Spain.
FAU - Lucena, M Isabel
AU  - Lucena MI
AUID- ORCID: 0000-0001-9586-4896
AD  - Unidad de Gestion Clinica de Gastroenterologia, Servicio de Farmacologia Clinica, 
      Instituto de Investigacion Biomedica de Malaga-IBIMA, Hospital Universitario 
      Virgen de la Victoria, Universidad de Malaga, CIBERehd, 29071 Malaga, Spain.
FAU - Cubero, Francisco Javier
AU  - Cubero FJ
AUID- ORCID: 0000-0003-1499-650X
AD  - Department of Immunology, Ophthalmology and ENT, Complutense University School of 
      Medicine, 28040 Madrid, Spain.
AD  - 12 de Octubre Health Research Institute (imas12), 28041 Madrid, Spain.
LA  - eng
GR  - SAF2016-78711/MINECO Retos/
GR  - EXOHEP-CM S2017/BMD-3727/Comunidad de Madrid/
GR  - NanoLiver-CM Y2018/NMT-4949/Comunidad de Madrid/
GR  - Ref. EA 18/14/ERAB/
GR  - 2018/117/AMMF/
GR  - 25/2019/UCM/
GR  - FIS-FEDER PI16_01748/FIS/
GR  - PI19-00883/PI/
GR  - UMA18-FEDERJA-194/UMA/
GR  - PY18-3364_PY19/PY/
GR  - RYC-2014-15242/MINECO/
GR  - 42/2018/Gilead Liver Research 2018/
GR  - CA17112/COST/
PT  - Journal Article
PT  - Review
DEP - 20210305
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8000729
OTO - NOTNLM
OT  - DILI
OT  - biomarkers
OT  - mechanisms
OT  - oxidative stress
OT  - risk factors
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/04/04 06:01
PMCR- 2021/03/05
CRDT- 2021/04/03 01:27
PHST- 2021/02/23 00:00 [received]
PHST- 2021/03/02 00:00 [accepted]
PHST- 2021/04/03 01:27 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/04/04 06:01 [medline]
PHST- 2021/03/05 00:00 [pmc-release]
AID - antiox10030390 [pii]
AID - antioxidants-10-00390 [pii]
AID - 10.3390/antiox10030390 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Mar 5;10(3):390. doi: 10.3390/antiox10030390.