Cargando…
Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice
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 DI...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000729/ https://www.ncbi.nlm.nih.gov/pubmed/33807700 http://dx.doi.org/10.3390/antiox10030390 |
_version_ | 1783671064515051520 |
---|---|
author | Villanueva-Paz, Marina Morán, Laura López-Alcántara, Nuria Freixo, Cristiana Andrade, Raúl J. Lucena, M Isabel Cubero, Francisco Javier |
author_facet | Villanueva-Paz, Marina Morán, Laura López-Alcántara, Nuria Freixo, Cristiana Andrade, Raúl J. Lucena, M Isabel Cubero, Francisco Javier |
author_sort | Villanueva-Paz, Marina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8000729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80007292021-03-28 Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice Villanueva-Paz, Marina Morán, Laura López-Alcántara, Nuria Freixo, Cristiana Andrade, Raúl J. Lucena, M Isabel Cubero, Francisco Javier Antioxidants (Basel) Review 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. MDPI 2021-03-05 /pmc/articles/PMC8000729/ /pubmed/33807700 http://dx.doi.org/10.3390/antiox10030390 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Review Villanueva-Paz, Marina Morán, Laura López-Alcántara, Nuria Freixo, Cristiana Andrade, Raúl J. Lucena, M Isabel Cubero, Francisco Javier Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice |
title | Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice |
title_full | Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice |
title_fullStr | Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice |
title_full_unstemmed | Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice |
title_short | Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice |
title_sort | oxidative stress in drug-induced liver injury (dili): from mechanisms to biomarkers for use in clinical practice |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000729/ https://www.ncbi.nlm.nih.gov/pubmed/33807700 http://dx.doi.org/10.3390/antiox10030390 |
work_keys_str_mv | AT villanuevapazmarina oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice AT moranlaura oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice AT lopezalcantaranuria oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice AT freixocristiana oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice AT andraderaulj oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice AT lucenamisabel oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice AT cuberofranciscojavier oxidativestressindruginducedliverinjurydilifrommechanismstobiomarkersforuseinclinicalpractice |