Skip to content
DraconiticResearch
Search Sources API
197,693 studies31 sourcesUpdated 14 min ago
Peer-reviewedCC BYBMC Pharmacology and Toxicology

Epinephrine-mediated sensitization of thioredoxin 1 enhances chlorpromazine protection against acute hepatotoxicity

  • Mohamed Hessien1
  • Thoria Donia1
  • Sherien Khedr2
  • Elsayed I. Salim3
  • Mariam M. Shamaa2
  • Doha F. Ismail1
  • Maha Hammady4
  • Mahesh Thirunavukkarasu5
  • Andrea Watters5
  • Nicole Taylor5
  • Ashraf Tabll6
  • Mai H. Hassan1
1 more authors
  • Nilanjana Maulik5
6 affiliations
  1. 1Molecular Cell Biology Unit, Division of Biochemistry, Faculty of Science, Tanta University
  2. 2Clinical and Biological Sciences Division, Biochemistry Department, Arab Academy for Science, Technology and Maritime Transport
  3. 3Molecular Carcinogenesis Laboratory, Department of Zoology, Faculty of Science, Tanta University
  4. 4Histology and Cell Biology Department, Faculty of Medicine, Alexandria University
  5. 5Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, School of Medicine, University of Connecticut
  6. 6Immunology Department,Egypt Center for Research and Regenerative Medicine (ECRRM)
Read full textDOICite

Abstract

Acute liver injury (ALI) is characterised by rapid hepatic necrosis and compromised liver functions. Drug-induced ALI, in particular, is associated with glutathione depletion and overproduction of reactive oxygen species (ROS). These alterations highlight the contribution of the thioredoxin system (Trx/TrxR/NADPH) in preserving hepatic redox homeostasis. Previously, we demonstrated that thioredoxin-1 (Trx1) overexpression exerts protective effects against ischemic heart and peripheral vascular disease. Also, the neuroprotective role of thioredoxin reductase (TrxR1) has been reported in Parkinson’s Disease. However, it remains unclear whether epinephrine (EP)-mediated boosting of the thioredoxin system, together with chlorpromazine (CPZ), provides sufficient protection against drug-induced ALI. To investigate this hypothesis, C57BL/6 mice were chronically administered a low dose of EP to enhance the expression of Trx1/TrxR1, followed by ALI induction with N-acetyl-para-aminophenol (APAP) and treatment with a subtoxic dose of CPZ. In parallel, hepatoma cell lines were treated with EP and/or CPZ to monitor the associated subcellular and molecular changes. The results showed that EP enhanced the expression of Trx1, thioredoxin-like protein 1 (TrxL1), and TrxR1 in liver and TrxR1 in hepatoma cell lines. Also, EP attenuated liver injury and enhanced the therapeutic effect of CPZ in ALI mice. A significant improvement in liver biomarkers, resolution of inflammation, attenuated oxidative stress, and restoration of hepatic histological architecture accompanied these observations. Moreover, activation of the thioredoxin system in hepatoma cells was associated with overexpression of β-arrestin1, TrxL1, and cAMP-response element-binding protein (CREB1), mirroring their involvement in Trx-mediated protection. Conclusively, these results addressed the protective role of boosting the cytosolic thioredoxin system in drug-induced ALI. Graphical Abstract

Related

  1. Effect of 1-min versus 3-min epinephrine dosing regimens on 48-h survival in a porcine cardiac arrest model
    Gyo Jin Ahn, Junghun Lee, Young‐II Roh +5
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textGeneral medicineCrossref
  2. Systemic epinephrine toxicity following topical epinephrine gauze use during burn debridement
    Honoka Hiki, Tomotaka Takanosu, Chikara Yonekawa +1
    Turkish Journal of Emergency MedicinePeer-reviewedCC BY-NC-SA 4.0Full textEpidemiology & public healthPMC
  3. Thioredoxin system: mechanisms and therapeutic potential in mental disorders
    Le Zhang, Xin Wang, Ningning Guo +1
    Frontiers in pharmacologyPeer-reviewedCC BYFull textPharmacology & toxicologyEurope PMC
  4. Local Anesthetic Systemic Toxicity Following High-Volume Ropivacaine, Epinephrine, Clonidine, and Ketorolac (RECK) Infiltration During Total Knee Arthroplasty: A Case Report.
    Brian Mendelson, Jose Perdomo Trejo, Soliana Bekele
    CureusPeer-reviewedCC BYFull textSurgery & anaesthesiaEurope PMC
  5. Changes of thioredoxin, oxidative stress markers, inflammation and muscle/renal damage following intensive endurance exercise
    Kaoru Sugama, Katsuhiko Suzuki, Kayo Yoshitani +5
    PubMedPeer-reviewedLicence not stated51 citedPhysiologyOpenAlex

Cite

BibTeXRIS
BibTeX
@article{hessien2026epinephrinemediated,
  title = {{Epinephrine-mediated sensitization of thioredoxin 1 enhances chlorpromazine protection against acute hepatotoxicity}},
  author = {Mohamed Hessien and Thoria Donia and Sherien Khedr and Elsayed I. Salim and Mariam M. Shamaa and Doha F. Ismail and Maha Hammady and Mahesh Thirunavukkarasu and Andrea Watters and Nicole Taylor and Ashraf Tabll and Mai H. Hassan and Nilanjana Maulik},
  journal = {BMC Pharmacology and Toxicology},
  year = {2026},
  month = oct,
  doi = {10.1186/s40360-026-01225-w},
  url = {https://doi.org/10.1186/s40360-026-01225-w},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Epinephrine-mediated sensitization of thioredoxin 1 enhances chlorpromazine protection against acute hepatotoxicity
AU  - Mohamed Hessien
AU  - Thoria Donia
AU  - Sherien Khedr
AU  - Elsayed I. Salim
AU  - Mariam M. Shamaa
AU  - Doha F. Ismail
AU  - Maha Hammady
AU  - Mahesh Thirunavukkarasu
AU  - Andrea Watters
AU  - Nicole Taylor
AU  - Ashraf Tabll
AU  - Mai H. Hassan
AU  - Nilanjana Maulik
PY  - 2026
DA  - 2026/10/25
JO  - BMC Pharmacology and Toxicology
DO  - 10.1186/s40360-026-01225-w
UR  - https://doi.org/10.1186/s40360-026-01225-w
AB  - Acute liver injury (ALI) is characterised by rapid hepatic necrosis and compromised liver functions. Drug-induced ALI, in particular, is associated with glutathione depletion and overproduction of reactive oxygen species (ROS). These alterations highlight the contribution of the thioredoxin system (Trx/TrxR/NADPH) in preserving hepatic redox homeostasis. Previously, we demonstrated that thioredoxin-1 (Trx1) overexpression exerts protective effects against ischemic heart and peripheral vascular disease. Also, the neuroprotective role of thioredoxin reductase (TrxR1) has been reported in Parkinson’s Disease. However, it remains unclear whether epinephrine (EP)-mediated boosting of the thioredoxin system, together with chlorpromazine (CPZ), provides sufficient protection against drug-induced ALI. To investigate this hypothesis, C57BL/6 mice were chronically administered a low dose of EP to enhance the expression of Trx1/TrxR1, followed by ALI induction with N-acetyl-para-aminophenol (APAP) and treatment with a subtoxic dose of CPZ. In parallel, hepatoma cell lines were treated with EP and/or CPZ to monitor the associated subcellular and molecular changes. The results showed that EP enhanced the expression of Trx1, thioredoxin-like protein 1 (TrxL1), and TrxR1 in liver and TrxR1 in hepatoma cell lines. Also, EP attenuated liver injury and enhanced the therapeutic effect of CPZ in ALI mice. A significant improvement in liver biomarkers, resolution of inflammation, attenuated oxidative stress, and restoration of hepatic histological architecture accompanied these observations. Moreover, activation of the thioredoxin system in hepatoma cells was associated with overexpression of β-arrestin1, TrxL1, and cAMP-response element-binding protein (CREB1), mirroring their involvement in Trx-mediated protection. Conclusively, these results addressed the protective role of boosting the cytosolic thioredoxin system in drug-induced ALI. Graphical Abstract
SN  - 2050-6511
ER  -