Role of oxidative stress and endoplasmic reticulum stress in drug-induced liver injury

The pathogenesis of drug-induced liver injury (DILI) is still in an early stage of research. However, investigators have shown that both oxidative stress and endoplasmic reticulum (ER) stress play a significant role in the pathological mechanism. However, there is little in-depth literature about these two mechanisms. In order to prevent and improve the clinical symptoms of DILI, it is particularly important to study its pathogenesis. In this review article, the role of ER and oxidative stress in DILI is thoroughly discussed.

[1]  Kui Wang,et al.  Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals , 2023, Pharmaceuticals.

[2]  E. Mostafavi,et al.  Genetic Diversity of Coxiella burnetii in Iran by Multi-Spacer Sequence Typing , 2022, Pathogens.

[3]  H. Jaeschke,et al.  Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice. , 2022, Journal of natural products.

[4]  Bingyu Ye,et al.  Mitochondrial Dysfunction and Chronic Liver Disease , 2022, Current issues in molecular biology.

[5]  H. Jaeschke,et al.  The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice. , 2022, Toxicology and applied pharmacology.

[6]  R. Teschke,et al.  Liver Injury in COVID-19 Patients with Drugs as Causatives: A Systematic Review of 996 DILI Cases Published 2020/2021 Based on RUCAM as Causality Assessment Method , 2022, International journal of molecular sciences.

[7]  G. Tiegs,et al.  TNF in the liver: targeting a central player in inflammation , 2022, Seminars in Immunopathology.

[8]  R. Andrade,et al.  Genetic and pharmacological inhibition of XBP1 protects against APAP hepatotoxicity through the activation of autophagy , 2022, Cell Death & Disease.

[9]  H. Jaeschke,et al.  Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose , 2022, Archives of Toxicology.

[10]  Ping Zhang,et al.  Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs , 2021, Chinese Medicine.

[11]  Huan Chen,et al.  Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model , 2021, BioMed research international.

[12]  H. Jaeschke,et al.  Recommendations for the use of the acetaminophen hepatotoxicity model for mechanistic studies and how to avoid common pitfalls , 2021, Acta pharmaceutica Sinica. B.

[13]  Tiangang Li,et al.  Autophagy in liver diseases: A review. , 2021, Molecular aspects of medicine.

[14]  K. Kuča,et al.  Hypothesis: JNK signaling is a therapeutic target of neurodegenerative diseases , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[15]  R. Andrade,et al.  Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice , 2021, Antioxidants.

[16]  H. Jaeschke,et al.  Ferroptosis and Acetaminophen Hepatotoxicity - Are We Going Down Another Rabbit Hole? , 2021, Gene expression.

[17]  H. Jaeschke,et al.  Mitochondrial Membrane Potential Drives Early Change in Mitochondrial Morphology After Acetaminophen Exposure. , 2021, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  H. Jaeschke,et al.  Mitochondrial Protein Adduct and Superoxide Generation are Prerequisites for Early Activation of c-Jun N-terminal Kinase within the Cytosol after an Acetaminophen Overdose in Mice. , 2020, Toxicology letters.

[19]  G. Long,et al.  Personality traits predict regression of pelvic girdle pain after pregnancy: a longitudinal follow-up study , 2020, BMC Pregnancy and Childbirth.

[20]  T. Rodrigues,et al.  Therapeutic potential of targeting mitochondrial dynamics in cancer. , 2020, Biochemical pharmacology.

[21]  Feng Zhang,et al.  Endoplasmic reticulum stress and protein degradation in chronic liver disease. , 2020, Pharmacological research.

[22]  C. Stephens,et al.  Drug induced liver injury: an update , 2020, Archives of Toxicology.

[23]  R. Teschke,et al.  Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues , 2020, Annals of translational medicine.

[24]  I. Scott,et al.  Calreticulin expression in human cardiac myocytes induces ER stress‐associated apoptosis , 2020, Physiological reports.

[25]  J. Lemasters,et al.  Suppression of iron mobilization from lysosomes to mitochondria attenuates liver injury after acetaminophen overdose in vivo in mice: Protection by minocycline. , 2020, Toxicology and applied pharmacology.

[26]  N. Sussman,et al.  Drug-Induced Liver Injury in the Setting of Analgesic Use. , 2020, Clinics in liver disease.

[27]  N. Sata,et al.  Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure , 2020, Cell Death & Disease.

[28]  J. Abe,et al.  Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress , 2020, Biomolecules.

[29]  B. Fromenty Alteration of mitochondrial DNA homeostasis in drug-induced liver injury. , 2020, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[30]  W. Ding,et al.  Role of autophagy in alcohol and drug-induced liver injury. , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[31]  Marcus Conrad,et al.  The chemical basis of ferroptosis , 2019, Nature Chemical Biology.

[32]  P. Watkins,et al.  Drug-induced liver injury , 2019, Nature Reviews Disease Primers.

[33]  R. Andrade,et al.  Endoplasmic Reticulum Stress-induced Upregulation of STARD1 Promotes Acetaminophen-induced Acute Liver Failure. , 2019, Gastroenterology.

[34]  R. Green,et al.  Endoplasmic reticulum stress and liver diseases. , 2019, Liver research.

[35]  C. Trautwein,et al.  Unfolded protein response is an early, non-critical event during hepatic stellate cell activation , 2019, Cell Death & Disease.

[36]  A. Jeyasekharan,et al.  ROS and the DNA damage response in cancer , 2018, Redox biology.

[37]  N. Kaplowitz,et al.  The Regulation of JNK Signaling Pathways in Cell Death through the Interplay with Mitochondrial SAB and Upstream Post-Translational Effects , 2018, International journal of molecular sciences.

[38]  T. Asselah,et al.  Mitochondrial Dysfunction and Signaling in Chronic Liver Diseases. , 2018, Gastroenterology.

[39]  G. Kroemer,et al.  Bax inhibitor‐1 protects from nonalcoholic steatohepatitis by limiting inositol‐requiring enzyme 1 alpha signaling in mice , 2018, Hepatology.

[40]  H. Jaeschke,et al.  Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives , 2018, Journal of clinical and translational research.

[41]  A. Moles,et al.  Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity , 2018, Front. Pharmacol..

[42]  H. Jaeschke,et al.  4-Methylpyrazole protects against acetaminophen hepatotoxicity in mice and in primary human hepatocytes , 2018, Human & experimental toxicology.

[43]  N. Kaplowitz,et al.  New insights into the role and mechanism of c‐Jun‐N‐terminal kinase signaling in the pathobiology of liver diseases , 2018, Hepatology.

[44]  Hongbo Hu,et al.  Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions , 2018, Redox biology.

[45]  F. Cubero,et al.  Dissecting the molecular pathophysiology of drug-induced liver injury , 2018, World journal of gastroenterology.

[46]  J. Auwerx,et al.  Repairing Mitochondrial Dysfunction in Disease. , 2018, Annual review of pharmacology and toxicology.

[47]  B. Karahalil,et al.  Hepatotoxicity associated with statins , 2017, Arhiv za higijenu rada i toksikologiju.

[48]  M. E. Solesio,et al.  From ATP synthase dimers to C-ring conformational changes: unified model of the mitochondrial permeability transition pore , 2017, Cell Death & Disease.

[49]  A. Bitto,et al.  Oxidative Stress: Harms and Benefits for Human Health , 2017, Oxidative medicine and cellular longevity.

[50]  N. Kaplowitz,et al.  Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis , 2017, International journal of molecular sciences.

[51]  W. Cong,et al.  CSH guidelines for the diagnosis and treatment of drug-induced liver injury , 2017, Hepatology International.

[52]  Hongbo Hu,et al.  Antcin H Protects Against Acute Liver Injury Through Disruption of the Interaction of c-Jun-N-Terminal Kinase with Mitochondria. , 2017, Antioxidants & redox signaling.

[53]  R. Venkataramanan,et al.  Drug Metabolism in the Liver. , 2017, Clinics in liver disease.

[54]  Andreas Koulovasilopoulos,et al.  Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver , 2017, Scientific Reports.

[55]  H. Jaeschke,et al.  Editor's Highlight: Metformin Protects Against Acetaminophen Hepatotoxicity by Attenuation of Mitochondrial Oxidant Stress and Dysfunction. , 2016, Toxicological sciences : an official journal of the Society of Toxicology.

[56]  Mitchell R. McGill,et al.  Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice. , 2016, Journal of hepatology.

[57]  William M. Lee,et al.  Clinical Features and Outcomes of Complementary and Alternative Medicine Induced Acute Liver Failure and Injury , 2016, The American Journal of Gastroenterology.

[58]  C. Muñoz-Pinedo,et al.  Cell death induced by endoplasmic reticulum stress , 2016, The FEBS journal.

[59]  N. Kaplowitz,et al.  c‐Jun N‐terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)‐dependent pathway leading to inactivation of intramitochondrial Src , 2016, Hepatology.

[60]  D. Hay,et al.  Reducing Hepatocyte Injury and Necrosis in Response to Paracetamol Using Noncoding RNAs , 2016, Stem cells translational medicine.

[61]  T. Luedde,et al.  Combined Activities of JNK1 and JNK2 in Hepatocytes Protect Against Toxic Liver Injury. , 2016, Gastroenterology.

[62]  Ning Wang,et al.  The Role of Oxidative Stress and Antioxidants in Liver Diseases , 2015, International journal of molecular sciences.

[63]  Z. Liu,et al.  Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate , 2015, Cell Death and Disease.

[64]  N. Kaplowitz,et al.  Targeting signal transduction pathways which regulate necrosis in acetaminophen hepatotoxicity. , 2015, Journal of hepatology.

[65]  M. Franco,et al.  Reactive nitrogen species in cellular signaling , 2015, Experimental biology and medicine.

[66]  U. Boelsterli,et al.  Targeting mitochondria with methylene blue protects mice against acetaminophen‐induced liver injury , 2015, Hepatology.

[67]  R. Radi,et al.  Metal-catalyzed protein tyrosine nitration in biological systems , 2014, Redox report : communications in free radical research.

[68]  G. Groothuis,et al.  Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity. , 2014, Toxicological sciences : an official journal of the Society of Toxicology.

[69]  R. Urrutia,et al.  Acetaminophen and NAPQI are toxic to auditory cells via oxidative and endoplasmic reticulum stress-dependent pathways , 2014, Hearing Research.

[70]  M. Michalak,et al.  The many functions of the endoplasmic reticulum chaperones and folding enzymes , 2014, IUBMB life.

[71]  P. Domingos,et al.  Physiological roles of regulated Ire1 dependent decay , 2014, Front. Genet..

[72]  M. Duchen,et al.  Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health , 2014, Biochimica et biophysica acta.

[73]  N. Kaplowitz,et al.  JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death , 2014, Cell Death and Disease.

[74]  F. Brandizzi,et al.  IRE1: ER stress sensor and cell fate executor. , 2013, Trends in cell biology.

[75]  Takao Iwawaki,et al.  CHOP is a critical regulator of acetaminophen-induced hepatotoxicity. , 2013, Journal of hepatology.

[76]  M. Mcphail,et al.  Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. , 2013, Journal of hepatology.

[77]  C. Vascotto,et al.  Alterations in the redox state and liver damage: hints from the EASL Basic School of Hepatology. , 2013, Journal of hepatology.

[78]  A. Jaeschke,et al.  Critical Role for Mixed-Lineage Kinase 3 in Acetaminophen-Induced Hepatotoxicity , 2012, Molecular Pharmacology.

[79]  D. Stolz,et al.  Parkin and Mitofusins Reciprocally Regulate Mitophagy and Mitochondrial Spheroid Formation* , 2012, The Journal of Biological Chemistry.

[80]  P. Walter,et al.  Structural basis of the unfolded protein response. , 2012, Annual review of cell and developmental biology.

[81]  Michael Karin,et al.  A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches. , 2012, Gastroenterology.

[82]  U. Förstermann,et al.  Nitric oxide synthases: regulation and function. , 2012, European heart journal.

[83]  L. Glimcher,et al.  IRE1α activation protects mice against acetaminophen-induced hepatotoxicity , 2012, The Journal of experimental medicine.

[84]  D. Pessayre,et al.  A variant in myeloperoxidase promoter hastens the emergence of hepatocellular carcinoma in patients with HCV-related cirrhosis. , 2012, Journal of hepatology.

[85]  D. Pessayre,et al.  Central role of mitochondria in drug-induced liver injury , 2012, Drug metabolism reviews.

[86]  Mitchell R. McGill,et al.  Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity , 2012, Drug metabolism reviews.

[87]  Hartmut Jaeschke,et al.  Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity , 2012, Liver international : official journal of the International Association for the Study of the Liver.

[88]  J. Varner,et al.  A review of the mammalian unfolded protein response , 2011, Biotechnology and bioengineering.

[89]  P. Walter,et al.  The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation , 2011, Science.

[90]  A. López-Guillermo,et al.  The expression of the endoplasmic reticulum stress sensor BiP/GRP78 predicts response to chemotherapy and determines the efficacy of proteasome inhibitors in diffuse large b-cell lymphoma. , 2011, The American journal of pathology.

[91]  Laurie H Glimcher,et al.  The unfolded protein response: integrating stress signals through the stress sensor IRE1α. , 2011, Physiological reviews.

[92]  P. Ganey,et al.  Animal models of idiosyncratic drug-induced liver injury—Current status , 2011, Critical reviews in toxicology.

[93]  N. Kaplowitz,et al.  c-Jun N-terminal Kinase (JNK)-dependent Acute Liver Injury from Acetaminophen or Tumor Necrosis Factor (TNF) Requires Mitochondrial Sab Protein Expression in Mice* , 2011, The Journal of Biological Chemistry.

[94]  K. Mishiba,et al.  Arabidopsis IRE1 catalyses unconventional splicing of bZIP60 mRNA to produce the active transcription factor , 2011, Scientific reports.

[95]  Bob van de Water,et al.  Diclofenac inhibits tumor necrosis factor‐α‐induced nuclear factor‐κB activation causing synergistic hepatocyte apoptosis , 2011, Hepatology.

[96]  P. Portincasa,et al.  Mitochondria in chronic liver disease. , 2011, Current drug targets.

[97]  B. Fromenty,et al.  Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. , 2011, Journal of hepatology.

[98]  L. MacMillan-Crow,et al.  Acetaminophen-Induced Hepatotoxicity in Mice Occurs with Inhibition of Activity and Nitration of Mitochondrial Manganese Superoxide Dismutase , 2011, Journal of Pharmacology and Experimental Therapeutics.

[99]  M. Karin,et al.  Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage , 2011, Annals of the rheumatic diseases.

[100]  L. Pearl,et al.  Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response , 2011, The EMBO journal.

[101]  H. Jaeschke,et al.  No evidence for caspase‐dependent apoptosis in acetaminophen hepatotoxicity , 2011, Hepatology.

[102]  P. Ganey,et al.  Intrinsic versus Idiosyncratic Drug-Induced Hepatotoxicity—Two Villains or One? , 2010, Journal of Pharmacology and Experimental Therapeutics.

[103]  C. Winterbourn,et al.  Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. , 2010, The Biochemical journal.

[104]  Eugenia Ulzurrun,et al.  Drug-induced liver injury: insights from genetic studies. , 2009, Pharmacogenomics.

[105]  C. Hetz,et al.  Fine-tuning of the unfolded protein response: Assembling the IRE1alpha interactome. , 2009, Molecular cell.

[106]  Chao Zhang,et al.  The unfolded protein response signals through high-order assembly of Ire1 , 2009, Nature.

[107]  C. Epstein,et al.  Prolonged ethanol administration depletes mitochondrial DNA in MnSOD-overexpressing transgenic mice, but not in their wild type littermates. , 2009, Toxicology and applied pharmacology.

[108]  R. Wek,et al.  Translational control and the unfolded protein response. , 2007, Antioxidants & redox signaling.

[109]  Hiderou Yoshida,et al.  Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. , 2007, Developmental cell.

[110]  Kazuhiro Nakamura,et al.  The c-jun kinase/stress-activated pathway: regulation, function and role in human disease. , 2007, Biochimica et biophysica acta.

[111]  U. Boelsterli,et al.  Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[112]  D. Pessayre,et al.  Tamoxifen Inhibits Topoisomerases, Depletes Mitochondrial DNA, and Triggers Steatosis in Mouse Liver , 2007, Journal of Pharmacology and Experimental Therapeutics.

[113]  G. Nagy,et al.  Acetaminophen induces ER dependent signaling in mouse liver. , 2007, Archives of biochemistry and biophysics.

[114]  Nicolas Locker,et al.  HCV and CSFV IRES domain II mediate eIF2 release during 80S ribosome assembly , 2007, The EMBO journal.

[115]  N. Kaplowitz,et al.  c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity. , 2006, Gastroenterology.

[116]  D. Pessayre,et al.  Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. , 2006, Mitochondrion.

[117]  H. Jaeschke,et al.  Peroxynitrite-Induced Mitochondrial and Endonuclease-Mediated Nuclear DNA Damage in Acetaminophen Hepatotoxicity , 2005, Journal of Pharmacology and Experimental Therapeutics.

[118]  Neil Kaplowitz,et al.  Idiosyncratic drug hepatotoxicity , 2005, Nature Reviews Drug Discovery.

[119]  R. Kaufman,et al.  ER stress and the unfolded protein response. , 2005, Mutation research.

[120]  R. Wek,et al.  Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[121]  H. Hirt,et al.  Reactive oxygen species: metabolism, oxidative stress, and signal transduction. , 2004, Annual review of plant biology.

[122]  H. Jaeschke,et al.  Role of lipid peroxidation as a mechanism of liver injury after acetaminophen overdose in mice. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[123]  D. Pessayre,et al.  Tacrine inhibits topoisomerases and DNA synthesis to cause mitochondrial DNA depletion and apoptosis in mouse liver , 2003, Hepatology.

[124]  N. Kaplowitz,et al.  Mechanisms for sensitization to TNF‐induced apoptosis by acute glutathione depletion in murine hepatocytes , 2003, Hepatology.

[125]  H. Jaeschke,et al.  Peroxynitrite Is a Critical Mediator of Acetaminophen Hepatotoxicity in Murine Livers: Protection by Glutathione , 2002, Journal of Pharmacology and Experimental Therapeutics.

[126]  K. Mori,et al.  XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor , 2001, Cell.

[127]  T. Aw,et al.  Gadd153 Sensitizes Cells to Endoplasmic Reticulum Stress by Down-Regulating Bcl2 and Perturbing the Cellular Redox State , 2001, Molecular and Cellular Biology.

[128]  M. Manns,et al.  I. TNF-induced liver injury. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[129]  G. Kajiyama,et al.  Acetaminophen-induced hepatic injury in mice: the role of lipid peroxidation and effects of pretreatment with coenzyme Q10 and alpha-tocopherol. , 1995, Free radical biology & medicine.

[130]  R. Radi,et al.  Desferrioxamine inhibition of the hydroxyl radical-like reactivity of peroxynitrite: role of the hydroxamic groups. , 1995, Free radical biology & medicine.

[131]  A. Wendel,et al.  Drug-induced lipid peroxidation in mice--I. Modulation by monooxygenase activity, glutathione and selenium status. , 1981, Biochemical pharmacology.

[132]  A Wendel,et al.  Acute paracetamol intoxication of starved mice leads to lipid peroxidation in vivo. , 1979, Biochemical pharmacology.

[133]  European Association for the Study of the Liver,et al.  EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease , 2016, Obesity Facts.

[134]  L. Liaudet,et al.  Nitric oxide and peroxynitrite in health and disease. , 2007, Physiological reviews.

[135]  R. Kaufman,et al.  A trip to the ER: coping with stress. , 2004, Trends in cell biology.

[136]  A. Wendel,et al.  Hepatic uptake and antihepatotoxic properties of vitamin E and liposomes in the mouse. , 1990, Chemico-biological interactions.