Oxidative Stress in Hepatic Diseases

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 21 November 2025 | Viewed by 1133

Special Issue Editor


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Guest Editor
Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain
Interests: natural products; polyphenols; nutrition; metabolic syndrome; obesity; biomarkers; inflammation; insulin resistance; ER stress; autophagy; NAFLD; circadian rhythms; microbiota; ROS; apoptosis

Special Issue Information

Dear Colleagues, 

The Special Issue "Oxidative Stress in Hepatic Diseases" focuses on the pivotal role of oxidative stress in the progression and pathology of various liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, viral hepatitis, and liver fibrosis. Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the liver's antioxidant defense systems, leading to cellular damage and inflammatory responses that drive liver disease progression. This issue aims to explore the mechanisms through which oxidative stress impacts hepatic health, including mitochondrial dysfunction, lipid peroxidation, and inflammatory cascades. We invite research on the molecular pathways involved, the identification of novel biomarkers for early diagnosis, and potential therapeutic strategies targeting oxidative stress. Through both original research and review articles, this Special Issue seeks to provide insights into innovative approaches to reduce oxidative damage, improve liver function, and ultimately enhance patient outcomes in hepatic disease management.

Dr. Miquel Mulero
Guest Editor

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Keywords

  • oxidative stress
  • hepatic diseases
  • liver fibrosis
  • reactive oxygen species (ROS)
  • mitochondrial dysfunction
  • lipid peroxidation
  • antioxidant defense
  • non-alcoholic fatty liver disease (NAFLD)
  • alcoholic liver disease
  • hepatoprotective strategies

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Published Papers (1 paper)

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Research

25 pages, 6489 KiB  
Article
The PERK-eIF2α-ATF4 Axis Is Involved in Mediating ER-Stress-Induced Ferroptosis via DDIT4-mTORC1 Inhibition and Acetaminophen-Induced Hepatotoxicity
by Thu-Hang Thi Nghiem, Kim Anh Nguyen, Fedho Kusuma, Soyoung Park, Jeongmin Park, Yeonsoo Joe, Jaeseok Han and Hun Taeg Chung
Antioxidants 2025, 14(3), 307; https://doi.org/10.3390/antiox14030307 - 3 Mar 2025
Viewed by 937
Abstract
Ferroptosis, a regulated form of cell death characterized by lipid peroxidation and iron accumulation, is increasingly recognized for its role in disease pathogenesis. The unfolded protein response (UPR) has been implicated in both endoplasmic reticulum (ER) stress and ferroptosis-mediated cell fate decisions; yet, [...] Read more.
Ferroptosis, a regulated form of cell death characterized by lipid peroxidation and iron accumulation, is increasingly recognized for its role in disease pathogenesis. The unfolded protein response (UPR) has been implicated in both endoplasmic reticulum (ER) stress and ferroptosis-mediated cell fate decisions; yet, the specific mechanism remains poorly understood. In this study, we demonstrated that ER stress induced by tunicamycin and ferroptosis triggered by erastin both activate the UPR, leading to the induction of ferroptotic cell death. This cell death was mitigated by the application of chemical chaperones and a ferroptosis inhibitor. Among the three arms of the UPR, the PERK-eIF2α-ATF4 signaling axis was identified as a crucial mediator in this process. Mechanistically, the ATF4-driven induction of DDIT4 plays a pivotal role, facilitating ferroptosis via the inhibition of the mTORC1 pathway. Furthermore, acetaminophen (APAP)-induced hepatotoxicity was investigated as a model of eIF2α-ATF4-mediated ferroptosis. Our findings reveal that the inhibition of eIF2α-ATF4 or ferroptosis protects against APAP-induced liver damage, underscoring the therapeutic potential of targeting these pathways. Overall, this study not only clarifies the intricate role of the PERK-eIF2α-ATF4 axis in ER-stress-and erastin-induced ferroptosis but also extends these findings to a clinically relevant model, providing a foundation for potential therapeutic interventions in conditions characterized by dysregulated ferroptosis and ER stress. Full article
(This article belongs to the Special Issue Oxidative Stress in Hepatic Diseases)
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