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Antioxidants
Special Issues
Redox Signaling in Liver Diseases
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Redox Signaling in Liver 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: closed (25 March 2024) | Viewed by 13127

Special Issue Editors

Prof. Dr. Don-Kyu Kim

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Guest Editor
Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju, Republic of Korea
Interests: gene regulation; cell signaling; nuclear hormone receptor; transcription factor; transcriptional regulation; liver metabolism; metabolic disease
Special Issues, Collections and Topics in MDPI journals
Dr. Kamalakannan Radhakrishnan

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Guest Editor
Combinatorial Cancer Immunotherapy MRC, Clinical Vaccine R&D Center, Chonnam National University Medical School, Hwasun, Republic of Korea
Interests: oxidative-stress-induced DNA damage; role of antioxidants in DNA repair; hepatic energy homeostasis; non-alcoholic steatohepatitis; liver metabolism; metabolic dysregulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liver is a very active organ which maintains the biological homeostasis of human body by performing innumerable functions including, but not limited to, immune regulation, detoxification, iron storage, energy homeostasis, bile production, and the storage of vitamins/minerals. The maintenance of proper balance between reactive oxygen species (ROS) and antioxidants is essential for the normal functioning of the liver. Physiological redox signaling leads to the posttranscriptional modification of redox proteins, and plays an important role in maintaining the ROS–antioxidant balance within the biological system. Any fluctuations in redox signaling lead to the imbalance of ROS and antioxidant levels, causing oxidative stress, eventually leading to acute and chronic liver diseases. Redox medicines, that is, redox-based therapeutic strategies, are considered novel tools to treat/prevent oxidative-stress-induced liver diseases. Understanding the detailed molecular mechanisms and diverse factors regulating cellular redox signaling, and identifying targetable molecules to modulate redox signaling, are extremely advantageous in developing therapeutic interventions to prevent the progression of liver diseases.

For this Special Issue of Antioxidants titled “Redox Signaling in Liver Diseases”, we invite you to submit your latest original research findings or a review article highlighting the significance of redox signaling in liver diseases and therapeutic strategies to treat dysregulated redox signaling in liver diseases.

Prof. Dr. Don-Kyu Kim
Dr. Kamalakannan Radhakrishnan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • redox signaling
  • oxidative stress
  • liver diseases
  • gene regulation
  • antioxidants
  • redox-based therapeutic strategies
  • reactive oxygen species

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Published Papers (4 papers)

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Research

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17 pages, 4853 KiB  
Article
Mechanistic Understanding of Idiosyncratic Drug-Induced Hepatotoxicity Using Co-Cultures of Hepatocytes and Macrophages
by Estela Villanueva-Badenas, M. Teresa Donato and Laia Tolosa
Antioxidants 2023, 12(7), 1315; https://doi.org/10.3390/antiox12071315 - 21 Jun 2023
Cited by 1 | Viewed by 2792
Abstract
Hepatotoxicity or drug-induced liver injury (DILI) is a major safety issue in drug development as a primary reason for drug failure in clinical trials and the main cause for post-marketing regulatory measures like drug withdrawal. Idiosyncratic DILI (iDILI) is a patient-specific, multifactorial, and [...] Read more.
Hepatotoxicity or drug-induced liver injury (DILI) is a major safety issue in drug development as a primary reason for drug failure in clinical trials and the main cause for post-marketing regulatory measures like drug withdrawal. Idiosyncratic DILI (iDILI) is a patient-specific, multifactorial, and multicellular process that cannot be recapitulated in current in vitro models; thus, our major goal is to develop and fully characterize a co-culture system and to evaluate its suitability for predicting iDILI. For this purpose, we used human hepatoma HepG2 cells and macrophages differentiated from a monocyte cell line (THP-1) and established the appropriate co-culture conditions for mimicking an inflammatory environment. Then, mono-cultures and co-cultures were treated with model iDILI compounds (trovafloxacin, troglitazone) and their parent non-iDILI compounds (levofloxacin, rosiglitazone), and the effects on viability and the mechanisms implicated (i.e., oxidative stress induction) were analyzed. Our results show that co-culture systems including hepatocytes (HepG2) and other cell types (THP-1-derived macrophages) help to enhance the mechanistic understanding of iDILI, providing better hepatotoxicity predictions. Full article
(This article belongs to the Special Issue Redox Signaling in Liver Diseases)
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13 pages, 2381 KiB  
Article
Evaluation of the Effects of Chia (Salvia hispanica L.) Leaves Ethanolic Extracts Supplementation on Biochemical and Hepatic Markers on Diet-Induced Obese Mice
by Gabriela Maturana, Javiera Segovia, Claudio Olea-Azar, Ernesto Uribe-Oporto, Alejandra Espinosa and María Carolina Zúñiga-López
Antioxidants 2023, 12(5), 1108; https://doi.org/10.3390/antiox12051108 - 17 May 2023
Cited by 4 | Viewed by 4647
Abstract
Obesity is a significant health concern affecting 13% of the world’s population. It is often associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD), which can cause chronic inflammation in the liver and adipose tissue. Obese hepatocytes show increased lipid droplets and [...] Read more.
Obesity is a significant health concern affecting 13% of the world’s population. It is often associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD), which can cause chronic inflammation in the liver and adipose tissue. Obese hepatocytes show increased lipid droplets and lipid peroxidation, which can lead to the progression of liver damage. Polyphenols have been shown to have the ability to reduce lipid peroxidation, thereby promoting hepatocyte health. Chia leaves, a by-product of chia seed production, are a natural source of bioactive antioxidant compounds, such as cinnamic acids and flavonoids, which have antioxidant and anti-inflammatory properties. In this study, chia leaves’ ethanolic extracts of two seed phenotypes were tested on diet-induced obese mice to evaluate their therapeutic potential. Results show that the chia leaf extract positively affected insulin resistance and lipid peroxidation in the liver. In addition, the extract improved the HOMA-IR index compared to the obese control group, reducing the number and size of lipid droplets and lipid peroxidation. These results suggest that chia leaf extract may help treat insulin resistance and liver damage associated with MAFLD. Full article
(This article belongs to the Special Issue Redox Signaling in Liver Diseases)
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Review

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19 pages, 1645 KiB  
Review
Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches
by Tatjana Radosavljevic, Milica Brankovic, Janko Samardzic, Jasmina Djuretić, Dusan Vukicevic, Danijela Vucevic and Vladimir Jakovljevic
Antioxidants 2024, 13(8), 906; https://doi.org/10.3390/antiox13080906 - 26 Jul 2024
Viewed by 1623
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), encompasses a range of liver conditions from steatosis to nonalcoholic steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis of MASLD [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), encompasses a range of liver conditions from steatosis to nonalcoholic steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis of MASLD involves metabolic dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role of mitochondrial dysfunction in MASLD’s progression. Therapeutically, enhancing mitochondrial function has gained interest, along with lifestyle changes and pharmacological interventions targeting mitochondrial processes. The FDA’s approval of resmetirom for metabolic-associated steatohepatitis (MASH) with fibrosis marks a significant step. While resmetirom represents progress, further research is essential to understand MASLD-related mitochondrial dysfunction fully. Innovative strategies like gene editing and small-molecule modulators, alongside lifestyle interventions, can potentially improve MASLD treatment. Drug repurposing and new targets will advance MASLD therapy, addressing its increasing global burden. Therefore, this review aims to provide a better understanding of the role of mitochondrial dysfunction in MASLD and identify more effective preventive and treatment strategies. Full article
(This article belongs to the Special Issue Redox Signaling in Liver Diseases)
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25 pages, 4826 KiB  
Review
Rising Influence of Nanotechnology in Addressing Oxidative Stress-Related Liver Disorders
by Sathiyamoorthy Padmanaban, Durgasruthi Pully, Antony V. Samrot, Vijayakumar Gosu, Nanthini Sadasivam, In-Kyu Park, Kamalakannan Radhakrishnan and Don-Kyu Kim
Antioxidants 2023, 12(7), 1405; https://doi.org/10.3390/antiox12071405 - 9 Jul 2023
Cited by 6 | Viewed by 3193
Abstract
Reactive oxygen species (ROS) play a significant role in the survival and decline of various biological systems. In liver-related metabolic disorders such as steatohepatitis, ROS can act as both a cause and a consequence. Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are two [...] Read more.
Reactive oxygen species (ROS) play a significant role in the survival and decline of various biological systems. In liver-related metabolic disorders such as steatohepatitis, ROS can act as both a cause and a consequence. Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are two distinct types of steatohepatitis. Recently, there has been growing interest in using medications that target ROS formation and reduce ROS levels as a therapeutic approach for oxidative stress-related liver disorders. Mammalian systems have developed various antioxidant defenses to protect against excessive ROS generation. These defenses modulate ROS through a series of reactions, limiting their potential impact. However, as the condition worsens, exogenous antioxidants become necessary to control ROS levels. Nanotechnology has emerged as a promising avenue, utilizing nanocomplex systems as efficient nano-antioxidants. These systems demonstrate enhanced delivery of antioxidants to the target site, minimizing leakage and improving targeting accuracy. Therefore, it is essential to explore the evolving field of nanotechnology as an effective means to lower ROS levels and establish efficient therapeutic interventions for oxidative stress-related liver disorders. Full article
(This article belongs to the Special Issue Redox Signaling in Liver Diseases)
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