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Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury

Drug-induced liver injury (DILI) is a widespread and harmful disease closely linked to mitochondrial and endoplasmic reticulum stress (ERS). Globally, severe drug-induced hepatitis, cirrhosis, and liver cancer are the primary causes of liver-related morbidity and mortality. A hallmark of DILI is ERS...

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Autores principales: Pu, Sisi, Pan, Yangyang, Zhang, Qian, You, Ting, Yue, Tao, Zhang, Yuxing, Wang, Meng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095764/
https://www.ncbi.nlm.nih.gov/pubmed/37049925
http://dx.doi.org/10.3390/molecules28073160
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author Pu, Sisi
Pan, Yangyang
Zhang, Qian
You, Ting
Yue, Tao
Zhang, Yuxing
Wang, Meng
author_facet Pu, Sisi
Pan, Yangyang
Zhang, Qian
You, Ting
Yue, Tao
Zhang, Yuxing
Wang, Meng
author_sort Pu, Sisi
collection PubMed
description Drug-induced liver injury (DILI) is a widespread and harmful disease closely linked to mitochondrial and endoplasmic reticulum stress (ERS). Globally, severe drug-induced hepatitis, cirrhosis, and liver cancer are the primary causes of liver-related morbidity and mortality. A hallmark of DILI is ERS and changes in mitochondrial morphology and function, which increase the production of reactive oxygen species (ROS) in a vicious cycle of mutually reinforcing stress responses. Several pathways are maladapted to maintain homeostasis during DILI. Here, we discuss the processes of liver injury caused by several types of drugs that induce hepatocyte stress, focusing primarily on DILI by ERS and mitochondrial stress. Importantly, both ERS and mitochondrial stress are mediated by the overproduction of ROS, destruction of Ca(2+) homeostasis, and unfolded protein response (UPR). Additionally, we review new pathways and potential pharmacological targets for DILI to highlight new possibilities for DILI treatment and mitigation.
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spelling pubmed-100957642023-04-13 Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury Pu, Sisi Pan, Yangyang Zhang, Qian You, Ting Yue, Tao Zhang, Yuxing Wang, Meng Molecules Review Drug-induced liver injury (DILI) is a widespread and harmful disease closely linked to mitochondrial and endoplasmic reticulum stress (ERS). Globally, severe drug-induced hepatitis, cirrhosis, and liver cancer are the primary causes of liver-related morbidity and mortality. A hallmark of DILI is ERS and changes in mitochondrial morphology and function, which increase the production of reactive oxygen species (ROS) in a vicious cycle of mutually reinforcing stress responses. Several pathways are maladapted to maintain homeostasis during DILI. Here, we discuss the processes of liver injury caused by several types of drugs that induce hepatocyte stress, focusing primarily on DILI by ERS and mitochondrial stress. Importantly, both ERS and mitochondrial stress are mediated by the overproduction of ROS, destruction of Ca(2+) homeostasis, and unfolded protein response (UPR). Additionally, we review new pathways and potential pharmacological targets for DILI to highlight new possibilities for DILI treatment and mitigation. MDPI 2023-04-02 /pmc/articles/PMC10095764/ /pubmed/37049925 http://dx.doi.org/10.3390/molecules28073160 Text en © 2023 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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Pu, Sisi
Pan, Yangyang
Zhang, Qian
You, Ting
Yue, Tao
Zhang, Yuxing
Wang, Meng
Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury
title Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury
title_full Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury
title_fullStr Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury
title_full_unstemmed Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury
title_short Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury
title_sort endoplasmic reticulum stress and mitochondrial stress in drug-induced liver injury
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095764/
https://www.ncbi.nlm.nih.gov/pubmed/37049925
http://dx.doi.org/10.3390/molecules28073160
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