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Antioxidants
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Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver...
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Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function

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 (31 January 2024) | Viewed by 31390

Special Issue Editor

Prof. Dr. Zhihui Feng

E-Mail Website
Guest Editor
Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Interests: obesity; diabetes; non-alcoholic fatty liver disease; aging; prenatal stress, age-related macular degeneration; mitochondrial dysfunction; oxidative stress; hypoxia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mitochondria are recognized as key regulators of cellular function. In particular, stressful events and situations cause alterations to energetic and metabolic homeostasis that are invariably traced back to perturbed mitochondrial function. One of the main culprits in mitochondrial dysfunction is the formation of oxidative species, which if prolonged, results in the overwhelming of intracellular defenses and thus results in oxidized mitochondrial components, causing the aforementioned dysfunction. Given its various roles in the organism, the liver heavily relies on mitochondrial oxidative phosphorylation to generate the vast amounts of ATP it requires for its daily needs, let alone when a hepatic insult is presented. As such, numerous research groups throughout the world have elected to investigate the role of oxidative stress in hepatic mitochondrial dysfunction, as well as identifying strategies and compounds that can preserve or restore mitochondrial and, concomitantly, organ function.

This Special Issue on the role of oxidative stress in hepatic mitochondrial function will publish work (both research work and review papers) on a broad range of research topics, ranging from pure toxicological events to metabolic diseases, surgical interventions, or strategic paradigms for transplantation, to name a few examples.

Prof. Dr. Zhihui Feng
Guest Editor

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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.

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Keywords

  • Liver bioenergetics
  • Mitochondrial dysfunction
  • Oxidative stress
  • Hepatic transplantation
  • Metabolic diseases

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Published Papers (7 papers)

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Editorial

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3 pages, 182 KiB  
Editorial
Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function
by Jie Xu and Zhihui Feng
Antioxidants 2023, 12(9), 1784; https://doi.org/10.3390/antiox12091784 - 20 Sep 2023
Cited by 2 | Viewed by 1602
Abstract
The traditional recognition of mitochondria as powerhouses that generate ATP and reactive oxygen species (ROS) via oxidative phosphorylation and the tricarboxylic acid cycle has ceased [...] Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)

Research

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16 pages, 3335 KiB  
Article
An Ethyl Acetate Extract of Eryngium carlinae Inflorescences Attenuates Oxidative Stress and Inflammation in the Liver of Streptozotocin-Induced Diabetic Rats
by Cristian M. Trejo-Hurtado, Cinthia I. Landa-Moreno, Jenaro Lemus-de la Cruz, Donovan J. Peña-Montes, Rocío Montoya-Pérez, Rafael Salgado-Garciglia, Salvador Manzo-Avalos, Christian Cortés-Rojo, Juan Luis Monribot-Villanueva, José Antonio Guerrero-Analco and Alfredo Saavedra-Molina
Antioxidants 2023, 12(6), 1235; https://doi.org/10.3390/antiox12061235 - 7 Jun 2023
Cited by 4 | Viewed by 2158
Abstract
Secondary metabolites such as flavonoids are promising in the treatment of non-alcoholic fatty liver disease (NAFLD), which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated regarding their medicinal [...] Read more.
Secondary metabolites such as flavonoids are promising in the treatment of non-alcoholic fatty liver disease (NAFLD), which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated regarding their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from streptozotocin (STZ)-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver triacylglycerides (TG) levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. We hypothesize that solvent polarity and consequently chemical composition of the ethyl acetate extract of E. carlinae, exert the beneficial effects due to phenolic compounds. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)
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Review

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25 pages, 3042 KiB  
Review
Liver Cell Mitophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis
by Jiaxin Chen, Linge Jian, Yangkun Guo, Chengwei Tang, Zhiyin Huang and Jinhang Gao
Antioxidants 2024, 13(6), 729; https://doi.org/10.3390/antiox13060729 - 15 Jun 2024
Cited by 2 | Viewed by 2995
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. MASLD and its advanced-stage liver fibrosis and cirrhosis are the leading causes of liver failure and liver-related death worldwide. Mitochondria are crucial organelles in liver cells for energy generation and [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. MASLD and its advanced-stage liver fibrosis and cirrhosis are the leading causes of liver failure and liver-related death worldwide. Mitochondria are crucial organelles in liver cells for energy generation and the oxidative metabolism of fatty acids and carbohydrates. Recently, mitochondrial dysfunction in liver cells has been shown to play a vital role in the pathogenesis of MASLD and liver fibrosis. Mitophagy, a selective form of autophagy, removes and recycles impaired mitochondria. Although significant advances have been made in understanding mitophagy in liver diseases, adequate summaries concerning the contribution of liver cell mitophagy to MASLD and liver fibrosis are lacking. This review will clarify the mechanism of liver cell mitophagy in the development of MASLD and liver fibrosis, including in hepatocytes, macrophages, hepatic stellate cells, and liver sinusoidal endothelial cells. In addition, therapeutic strategies or compounds related to hepatic mitophagy are also summarized. In conclusion, mitophagy-related therapeutic strategies or compounds might be translational for the clinical treatment of MASLD and liver fibrosis. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)
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25 pages, 1228 KiB  
Review
Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases
by Ivo F. Machado, Raul G. Miranda, Daniel J. Dorta, Anabela P. Rolo and Carlos M. Palmeira
Antioxidants 2023, 12(6), 1212; https://doi.org/10.3390/antiox12061212 - 3 Jun 2023
Cited by 25 | Viewed by 4278
Abstract
Reactive oxygen species (ROS) are important second messengers in many metabolic processes and signaling pathways. Disruption of the balance between ROS generation and antioxidant defenses results in the overproduction of ROS and subsequent oxidative damage to biomolecules and cellular components that disturb cellular [...] Read more.
Reactive oxygen species (ROS) are important second messengers in many metabolic processes and signaling pathways. Disruption of the balance between ROS generation and antioxidant defenses results in the overproduction of ROS and subsequent oxidative damage to biomolecules and cellular components that disturb cellular function. Oxidative stress contributes to the initiation and progression of many liver pathologies such as ischemia-reperfusion injury (LIRI), non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Therefore, controlling ROS production is an attractive therapeutic strategy in relation to their treatment. In recent years, increasing evidence has supported the therapeutic effects of polyphenols on liver injury via the regulation of ROS levels. In the current review, we summarize the effects of polyphenols, such as quercetin, resveratrol, and curcumin, on oxidative damage during conditions that induce liver injury, such as LIRI, NAFLD, and HCC. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)
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19 pages, 1228 KiB  
Review
Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review
by Antonio Paoli and Giuseppe Cerullo
Antioxidants 2023, 12(5), 1065; https://doi.org/10.3390/antiox12051065 - 8 May 2023
Cited by 31 | Viewed by 8546
Abstract
Together with the global rise in obesity and metabolic syndrome, the prevalence of individuals who suffer from nonalcoholic fatty liver disease (NAFLD) has risen dramatically. NAFLD is currently the most common chronic liver disease and includes a continuum of liver disorders from initial [...] Read more.
Together with the global rise in obesity and metabolic syndrome, the prevalence of individuals who suffer from nonalcoholic fatty liver disease (NAFLD) has risen dramatically. NAFLD is currently the most common chronic liver disease and includes a continuum of liver disorders from initial fat accumulation to nonalcoholic steatohepatitis (NASH), considered the more severe forms, which can evolve in, cirrhosis, and hepatocellular carcinoma. Common features of NAFLD includes altered lipid metabolism mainly linked to mitochondrial dysfunction, which, as a vicious cycle, aggravates oxidative stress and promotes inflammation and, as a consequence, the progressive death of hepatocytes and the severe form of NAFLD. A ketogenic diet (KD), i.e., a diet very low in carbohydrates (<30 g/die) that induces “physiological ketosis”, has been demonstrated to alleviate oxidative stress and restore mitochondrial function. Based on this, the aim of the present review is to analyze the body of evidence regarding the potential therapeutic role of KD in NAFLD, focusing on the interplay between mitochondria and the liver, the effects of ketosis on oxidative stress pathways, and the impact of KD on liver and mitochondrial function. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)
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21 pages, 757 KiB  
Review
Cardiac Hepatopathy: New Perspectives on Old Problems through a Prism of Endogenous Metabolic Regulations by Hepatokines
by Alexander A. Berezin, Zeljko Obradovic, Tetiana A. Berezina, Elke Boxhammer, Michael Lichtenauer and Alexander E. Berezin
Antioxidants 2023, 12(2), 516; https://doi.org/10.3390/antiox12020516 - 17 Feb 2023
Cited by 3 | Viewed by 4068
Abstract
Cardiac hepatopathy refers to acute or chronic liver damage caused by cardiac dysfunction in the absence of any other possible causative reasons of liver injury. There is a large number of evidence of the fact that cardiac hepatopathy is associated with poor clinical [...] Read more.
Cardiac hepatopathy refers to acute or chronic liver damage caused by cardiac dysfunction in the absence of any other possible causative reasons of liver injury. There is a large number of evidence of the fact that cardiac hepatopathy is associated with poor clinical outcomes in patients with acute or actually decompensated heart failure (HF). However, the currently dominated pathophysiological background does not explain a role of metabolic regulative proteins secreted by hepatocytes in progression of HF, including adverse cardiac remodeling, kidney injury, skeletal muscle dysfunction, osteopenia, sarcopenia and cardiac cachexia. The aim of this narrative review was to accumulate knowledge of hepatokines (adropin; fetuin-A, selenoprotein P, fibroblast growth factor-21, and alpha-1-microglobulin) as adaptive regulators of metabolic homeostasis in patients with HF. It is suggested that hepatokines play a crucial, causative role in inter-organ interactions and mediate tissue protective effects counteracting oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and necrosis. The discriminative potencies of hepatokines for HF and damage of target organs in patients with known HF is under on-going scientific discussion and requires more investigations in the future. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)
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25 pages, 2297 KiB  
Review
Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases
by Moon Nyeo Park, Md. Ataur Rahman, Md. Hasanur Rahman, Jong Woo Kim, Min Choi, Jeong Woo Kim, Jinwon Choi, Myunghan Moon, Kazi Rejvee Ahmed and Bonglee Kim
Antioxidants 2022, 11(10), 2041; https://doi.org/10.3390/antiox11102041 - 17 Oct 2022
Cited by 19 | Viewed by 5842
Abstract
Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and [...] Read more.
Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)
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