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Antioxidants
Special Issues
Oxidative Stress and Liver Disease
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Oxidative Stress and Liver Disease

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: 31 October 2025 | Viewed by 12089

Special Issue Editor

Dr. Alejandra Espinosa Escalona

E-Mail Website
Guest Editor
Center of Interdisciplinary Biomedical and Engineering Research for Health, Faculty of Medicine, Campus San Felipe, Universidad de Valparaíso, Valparaíso 2340000, Chile
Interests: antioxidants; liver diseases; insulin resistance

Special Issue Information

Dear Colleagues,

We are pleased to announce a Special Issue of Antioxidants that focuses on antioxidants and liver disease. Metabolic dysfunction-associated fatty liver disease (MAFLD), a term coined in 2018, has replaced nonalcoholic fatty liver disease (NAFLD). Chronic liver diseases of metabolic origin have diverse causes, including genetics, epigenetics, and the composition of the microbiota. Oxidative stress has been implicated in disease progression by several mechanisms associated with hepatocyte damage. The recent pandemic, which led to prolonged periods of lockdown and sedentary lifestyles, further exacerbated the risk factors of obesity and metabolic syndrome, both of which are associated with an increase in oxidative stress. All three contribute to liver disease progression, especially when combined with increased alcohol consumption, a lack of exercise, being elderly, and a number of other risk factors. We invite submissions to this Special Issue of original research articles, reviews, and case studies related to MAFLD, antioxidants, liver damage mechanisms, etc. Contributions exploring the latest advancements in our understanding of the pathogenesis, diagnosis, treatment, and prevention of liver disease are particularly welcome. We look forward to your valuable contributions to this important area of research.

Sincerely,

Dr. Alejandra Espinosa Escalona
Guest Editor

Manuscript Submission Information

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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

  • oxidative stress
  • antioxidants
  • MAFLD
  • NAFLD
  • obesity

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Published Papers (8 papers)

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Research

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26 pages, 5471 KiB  
Article
A Defective Circulating Mitochondrial Bioenergetics Profile Reflects the Hepatic One and Outlines Genetic MASLD
by Erika Paolini, Miriam Longo, Marica Meroni, Paola Podini, Marco Maggioni, Angelo Quattrini, Anna Ludovica Fracanzani and Paola Dongiovanni
Antioxidants 2025, 14(6), 618; https://doi.org/10.3390/antiox14060618 - 22 May 2025
Viewed by 62
Abstract
Genetics and mitochondrial (mt) dysfunction contribute to metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, we demonstrated that the co-presence of PNPLA3, TM6SF2 and MBOAT7 polymorphisms predisposes to disease progression in MASLD patients and that their deletion triggers mt maladaptation in vitro. Here, [...] Read more.
Genetics and mitochondrial (mt) dysfunction contribute to metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, we demonstrated that the co-presence of PNPLA3, TM6SF2 and MBOAT7 polymorphisms predisposes to disease progression in MASLD patients and that their deletion triggers mt maladaptation in vitro. Here, we deepened the impact of the silencing of these genes on mt dynamism and respiration by reintroducing TM6SF2 and/or MBOAT7 wild-type proteins in deleted cells through lentiviral infection. Since hepatic mt bioenergetics is impaired in MASLD, in the attempt to identify a non-invasive signature, we then compared the enzymatic mt activity of seahorses, which was assessed in liver biopsies and peripheral blood mononuclear cells (PBMCs) of biopsy-proven MASLD patients (n = 44; Discovery cohort) stratified according to the number of the three at-risk variants (3NRV). Concerning the in vitro results, the rescue of MBOAT7 and/or TM6SF2 wild-type proteins resulted in the assembly of spaghetti-shaped mitochondria with improved oxidative phosphorylation (OXPHOS) capacity. In the Discovery cohort, the hepatic bioenergetic profile fully reflected that in PBMCs and was impaired especially in 3NRV carriers. A lowered serum respiration rate was confirmed in noninvasively assessed MASLD (n = 45; Fibroscan-MASLD cohort), while it did not change in unrelated liver disease patients (n = 45). In summary, we firstly demonstrated that mt circulating respirometry reflects that in liver and is specific in defining genetic MASLD. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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30 pages, 7740 KiB  
Article
Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells
by Hui-Hsuan Lin, Pei-Rong Yu, Chiao-Yun Tseng, Ming-Shih Lee and Jing-Hsien Chen
Antioxidants 2025, 14(5), 595; https://doi.org/10.3390/antiox14050595 - 16 May 2025
Viewed by 152
Abstract
Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod [...] Read more.
Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment–insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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24 pages, 6948 KiB  
Article
Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models
by Gabriela Svobodová, Michaela Šadibolová, Eva Velecká, Lucia Mráziková, Petra Vaculová, Petra Matoušková, Jaroslav Kuneš, Lenka Maletínská and Iva Boušová
Antioxidants 2024, 13(11), 1371; https://doi.org/10.3390/antiox13111371 - 9 Nov 2024
Viewed by 1583
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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17 pages, 1995 KiB  
Article
A Case–Control Study Supports Genetic Contribution of the PON Gene Family in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease
by Evelien Van Dijck, Sara Diels, Erik Fransen, Tycho Canter Cremers, An Verrijken, Eveline Dirinck, Alexander Hoischen, Geert Vandeweyer, Wim Vanden Berghe, Luc Van Gaal, Sven Francque and Wim Van Hul
Antioxidants 2024, 13(9), 1051; https://doi.org/10.3390/antiox13091051 - 29 Aug 2024
Viewed by 1296
Abstract
The paraoxonase (PON) gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare [...] Read more.
The paraoxonase (PON) gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare PON variants on both conditions was investigated. A total of 507 healthy weight individuals and 744 patients with obesity including 433 with histological liver assessment, were sequenced with single-molecule molecular inversion probes (smMIPs), allowing the identification of genetic contributions to obesity and MASLD-related liver features. Polymorphisms rs705379 and rs854552 in the PON1 gene displayed significant association with MASLD stage and fibrosis, respectively. Additionally, rare PON1 variants were strongly associated with obesity. This study thereby reinforces the genetic foundation of PON1 in obesity and various MASLD-related liver features, by extending previous findings from common variants to include rare variants. Additionally, rare and very rare variants in PON2 were discovered to be associated with MASLD-related hepatic fibrosis. Notably, we are the first to report an association between naturally occurring rare PON2 variants and MASLD-related liver fibrosis. Considering the critical role of liver fibrosis in MASLD outcome, PON2 emerges as a possible candidate for future research endeavors including exploration of biomarker potential. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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18 pages, 955 KiB  
Article
Effects of a Two-Year Lifestyle Intervention on Intrahepatic Fat Reduction and Renal Health: Mitigation of Inflammation and Oxidative Stress, a Randomized Trial
by Maria Magdalena Quetglas-Llabrés, Margalida Monserrat-Mesquida, Cristina Bouzas, Silvia García, David Mateos, Miguel Casares, Cristina Gómez, Lucía Ugarriza, Josep A. Tur and Antoni Sureda
Antioxidants 2024, 13(7), 754; https://doi.org/10.3390/antiox13070754 - 21 Jun 2024
Cited by 3 | Viewed by 1844
Abstract
Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease observed in clinical practice worldwide. This disorder has been independently associated with an increased risk of developing chronic kidney disease (CKD). The aim of this study was to evaluate whether a [...] Read more.
Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease observed in clinical practice worldwide. This disorder has been independently associated with an increased risk of developing chronic kidney disease (CKD). The aim of this study was to evaluate whether a 2-year intervention based on a Mediterranean diet (MedDiet) and physical activity focussed on reducing intrahepatic fat contents (IFC) was associated with a decreased risk of CKD. Forty adults (50% women) residing in Mallorca, aged 48 to 60 years, diagnosed with MAFLD were recruited. Participants were divided into two groups based on whether they improved IFC measured by nuclear magnetic resonance. Anthropometric and clinical parameters improved in responders, including reduced weight, body mass index (BMI), and waist circumference. Only responders showed improvements in lipid profile and liver enzymes. Haematological parameters showed favourable changes in both groups. Oxidative stress and inflammatory biomarkers differed between groups. Responders had lower plasma interleukine-18 (IL-18) levels, but higher erythrocyte malonaldehyde (MDA) levels. Non-responders showed increased erythrocyte catalase and superoxide dismutase activity. After 2 years, non-responders had higher serum creatinine, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) levels, while responders showed reductions in these parameters together with uric acid and urine albumin-to-creatinine ratio (UACR). Positive correlations were found between changes in IFC and kidney injury biomarkers, including MDRD and serum creatinine levels. In conclusion, a healthy diet based on the Mediterranean dietary pattern and lifestyle promotes significant improvements in parameters related to cardiovascular, hepatic, and renal health. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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19 pages, 2509 KiB  
Article
The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study
by Florian Primavesi, Thomas Senoner, Sophie Schindler, Aleksandar Nikolajevic, Pietro Di Fazio, Georg Csukovich, Silvia Eller, Bettina Neumayer, Markus Anliker, Eva Braunwarth, Rupert Oberhuber, Thomas Resch, Manuel Maglione, Benno Cardini, Thomas Niederwieser, Silvia Gasteiger, Eckhard Klieser, Herbert Tilg, Stefan Schneeberger, Daniel Neureiter, Dietmar Öfner, Jakob Troppmair and Stefan Stättneradd Show full author list remove Hide full author list
Antioxidants 2024, 13(5), 590; https://doi.org/10.3390/antiox13050590 - 11 May 2024
Cited by 1 | Viewed by 1875
Abstract
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according [...] Read more.
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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Review

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13 pages, 1051 KiB  
Review
Myokines and Their Potential Protective Role Against Oxidative Stress in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by José Luis Bucarey, Isis Trujillo-González, Evan M. Paules and Alejandra Espinosa
Antioxidants 2024, 13(11), 1363; https://doi.org/10.3390/antiox13111363 - 7 Nov 2024
Cited by 3 | Viewed by 2763
Abstract
Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity [...] Read more.
Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity in preventing sarcopenia and mitigating metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review focuses on discussing the roles of specific myokines in activating intracellular signaling pathways within the liver, which confer protection against steatosis and lipid peroxidation. We detail the mechanism underlying lipid peroxidation and highlight the liver’s antioxidant defenses, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are pivotal in reducing ferroptosis. Furthermore, we provide an in-depth analysis of key myokines, including myostatin, brain-derived neurotrophic factor (BDNF), and irisin, among others, and their potential impact on liver function. Finally, we discuss the molecular mechanisms through which these myokines influence oxidate stress and lipid metabolism, emphasizing their capacity to modulate antioxidant responses in the liver. Finally, we underscore the therapeutic potential of exercise as a non-pharmacological intervention to enhance myokine release, thereby preventing the progression of MASD through improved hepatic antioxidant defenses. This review represents a comprehensive perspective on the intersection of exercise, myokine biology, and liver health. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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Other

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41 pages, 2889 KiB  
Systematic Review
Alterations in Glutathione Redox Homeostasis in Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review
by Lucia Cesarini, Flavia Grignaffini, Anna Alisi and Anna Pastore
Antioxidants 2024, 13(12), 1461; https://doi.org/10.3390/antiox13121461 - 28 Nov 2024
Viewed by 1531
Abstract
Low molecular weight (LMW) thiols, particularly glutathione, play pathogenic roles in various multiorgan diseases. The liver is central for the production and systemic distribution of LMW thiols; thus, it is particularly susceptible to the imbalance of redox status that may determine increased oxidative [...] Read more.
Low molecular weight (LMW) thiols, particularly glutathione, play pathogenic roles in various multiorgan diseases. The liver is central for the production and systemic distribution of LMW thiols; thus, it is particularly susceptible to the imbalance of redox status that may determine increased oxidative stress and trigger the liver damage observed in metabolic dysfunction-associated steatotic liver disease (MASLD) models and humans. Indeed, increased LMW thiols at the cellular and extracellular levels may be associated with the severity of MASLD. Here, we present a systematic literature review of recent studies assessing the levels of LMW thiols in MASLD in in vivo and in vitro models and human subjects. Based on the PRISMA 2020 criteria, a search was conducted using PubMed and Scopus by applying inclusion/exclusion filters. The initial search returned 1012 documents, from which 165 eligible studies were selected, further described, and qualitatively analysed. Of these studies, most focused on animal and cellular models, while a minority used human fluids. The analysis of these studies revealed heterogeneity in the methods of sample processing and measurement of LMW thiol levels, which hinder cut-off values for diagnostic use. Standardisation of the analysis and measure of LMW thiol is necessary to facilitate future studies. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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