10th Anniversary of Antioxidants—Review Collection

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 85922

Special Issue Editors


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Guest Editor
Department of Chemical Sciences, University of Naples “Federico II”, Via Cintia 4, I-80126 Naples, Italy
Interests: polyphenol antioxidants of dietary origin; conjugates of polyphenols with sulphydryl compounds of biological relevance; antioxidants from marine sources; valorization of agri food wastes; synthesis and exploitation of biopolymers from natural polyphenols; chemistry and structural investigation of natural polymers from catechols including human epidermal pigments melanins; oxidation chemistry of catecholamines in relation to neurodegenerative disorders; design and preparation of polydopamine related biomaterials with peculiar adhesive properties
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Guest Editor
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany
Interests: bioorganic chemistry; catalytic sensor/effector agents; epistemology; intracellular diagnostics; nanotechnology; natural products; reactive sulfur and selenium species; redox regulation via the cellular thiolstat
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is intended to celebrate the 10th anniversary of Antioxidants by gathering review articles representative of the importance that this field has reached over the last decade. Nowadays, the term antioxidants has acquired so many facets, covering natural antioxidants, synthetic compounds, oxidative stress conditions and associated diseases, redox modulation, antioxidant-based therapeutic approaches—in fact, it is actually impossible, if not futile, to draw up a comprehensive list. So, we may start from the historical definition by Halliwell and Gutteridge of an antioxidant as  “any substance that delays, prevents or removes oxidative damage to a target molecule” (Halliwell, B.; Gutteridge, J.M.C. Free Radicals in Biology and Medicine; Oxford University Press: Oxford, UK, 2015). For this Special Issue, we look forward to featuring review articles that contribute to updating and completing this viewpoint. The contributions we solicit in this issue are expected to review the recent advances in most diverse aspects of the field under an academic, industrial or clinical perspective. Moreover, the viewpoint of experts should guide the readers through the vast literature and indicate the right direction along which research should move in the near future. 

Prof. Dr. Alessandra Napolitano
Prof. Dr. Claus Jacob
Guest Editors

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.

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Published Papers (25 papers)

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24 pages, 584 KiB  
Review
N-acetylcysteine Pharmacology and Applications in Rare Diseases—Repurposing an Old Antioxidant
by Siddhee A. Sahasrabudhe, Marcia R. Terluk and Reena V. Kartha
Antioxidants 2023, 12(7), 1316; https://doi.org/10.3390/antiox12071316 - 21 Jun 2023
Cited by 2 | Viewed by 3512
Abstract
N-acetylcysteine (NAC), a precursor of cysteine and, thereby, glutathione (GSH), acts as an antioxidant through a variety of mechanisms, including oxidant scavenging, GSH replenishment, antioxidant signaling, etc. Owing to the variety of proposed targets, NAC has a long history of use as a [...] Read more.
N-acetylcysteine (NAC), a precursor of cysteine and, thereby, glutathione (GSH), acts as an antioxidant through a variety of mechanisms, including oxidant scavenging, GSH replenishment, antioxidant signaling, etc. Owing to the variety of proposed targets, NAC has a long history of use as a prescription product and in wide-ranging applications that are off-label as an over-the-counter (OTC) product. Despite its discovery in the early 1960s and its development for various indications, systematic clinical pharmacology explorations of NAC pharmacokinetics (PK), pharmacodynamic targets, drug interactions, and dose-ranging are sorely limited. Although there are anecdotal instances of NAC benefits in a variety of diseases, a comprehensive review of the use of NAC in rare diseases does not exist. In this review, we attempt to summarize the existing literature focused on NAC explorations in rare diseases targeting mitochondrial dysfunction along with the history of NAC usage, approved indications, mechanisms of action, safety, and PK characterization. Further, we introduce the research currently underway on other structural derivatives of NAC and acknowledge the continuum of efforts through pre-clinical and clinical research to facilitate further therapeutic development of NAC or its derivatives for rare diseases. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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16 pages, 2171 KiB  
Review
Diverse Possibilities of Si-Based Agent, a Unique New Antioxidant
by Yoshihisa Koyama, Yuki Kobayashi, Hikaru Kobayashi and Shoichi Shimada
Antioxidants 2023, 12(5), 1061; https://doi.org/10.3390/antiox12051061 - 08 May 2023
Cited by 2 | Viewed by 1630
Abstract
Antioxidant therapy is an effective approach for treating diseases in which oxidative stress is involved in the onset of symptoms. This approach aims to rapidly replenish the antioxidant substances in the body when they are depleted due to excess oxidative stress. Importantly, a [...] Read more.
Antioxidant therapy is an effective approach for treating diseases in which oxidative stress is involved in the onset of symptoms. This approach aims to rapidly replenish the antioxidant substances in the body when they are depleted due to excess oxidative stress. Importantly, a supplemented antioxidant must specifically eliminate harmful reactive oxygen species (ROS) without reacting with physiologically beneficial ROS, which are important to the body. In this regard, typically used antioxidant therapies can be effective, but may cause adverse effects due to their lack of specificity. We believe that Si-based agents are epoch-making drugs that can overcome these problems associated with current antioxidative therapy. These agents alleviate the symptoms of oxidative-stress-associated diseases by generating large amounts of the antioxidant hydrogen in the body. Moreover, Si-based agents are expected to be highly effective therapeutic drug candidates because they have anti-inflammatory, anti-apoptotic, and antioxidant effects. In this review, we discuss Si-based agents and their potential future applications in antioxidant therapy. There have been several reports of hydrogen generation from silicon nanoparticles, but unfortunately, none have been approved as pharmaceutical agents. Therefore, we believe that our research into medical applications using Si-based agents is a breakthrough in this research field. The knowledge obtained thus far from animal models of pathology may greatly contribute to the improvement of existing treatment methods and the development of new treatment methods. We hope that this review will further revitalize the research field of antioxidants and lead to the commercialization of Si-based agents. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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22 pages, 3485 KiB  
Review
Recent Applications of Melanin-like Nanoparticles as Antioxidant Agents
by Alexandra Mavridi-Printezi, Arianna Menichetti, Dario Mordini, Riccardo Amorati and Marco Montalti
Antioxidants 2023, 12(4), 863; https://doi.org/10.3390/antiox12040863 - 02 Apr 2023
Cited by 9 | Viewed by 3077
Abstract
Nanosized antioxidants are highly advantageous in terms of versatility and pharmacokinetics, with respect to conventional molecular ones. Melanin-like materials, artificial species inspired by natural melanin, combine recognized antioxidant (AOX) activity with a unique versatility of preparation and modification. Due to this versatility and [...] Read more.
Nanosized antioxidants are highly advantageous in terms of versatility and pharmacokinetics, with respect to conventional molecular ones. Melanin-like materials, artificial species inspired by natural melanin, combine recognized antioxidant (AOX) activity with a unique versatility of preparation and modification. Due to this versatility and documented biocompatibility, artificial melanin has been incorporated into a variety of nanoparticles (NP) in order to give new platforms for nanomedicine with enhanced AOX activity. In this review article, we first discuss the chemical mechanisms behind the AOX activity of materials in the context of the inhibition of the radical chain reaction responsible for the peroxidation of biomolecules. We also focus briefly on the AOX properties of melanin-like NP, considering the effect of parameters such as size, preparation methods and surface functionalization on them. Then, we consider the most recent and relevant applications of AOX melanin-like NPs that are able to counteract ferroptosis and be involved in the treatment of important diseases that affect, e.g., the cardiovascular and nervous systems, as well as the kidneys, liver and articulations. A specific section will be dedicated to cancer treatment, since the role of melanin in this context is still very debated. Finally, we propose future strategies in AOX development for a better chemical understanding of melanin-like materials. In particular, the composition and structure of these materials are still debated, and they present a high level of variability. Thus, a better understanding of the mechanism behind the interaction of melanin-like nanostructures with different radicals and highly reactive species would be highly advantageous for the design of more effective and specific AOX nano-agents. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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17 pages, 1237 KiB  
Review
Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection
by Jarosław Nuszkiewicz, Paweł Sutkowy, Marcin Wróblewski, Marta Pawłowska, Roland Wesołowski, Joanna Wróblewska and Alina Woźniak
Antioxidants 2023, 12(3), 733; https://doi.org/10.3390/antiox12030733 - 16 Mar 2023
Cited by 10 | Viewed by 2900
Abstract
Ferroptosis is a recently discovered form of programmed cell death. It is characterized by the accumulation of iron and lipid hydroperoxides in cells. Vitamin K is known to have antioxidant properties and plays a role in reducing oxidative stress, particularly in lipid cell [...] Read more.
Ferroptosis is a recently discovered form of programmed cell death. It is characterized by the accumulation of iron and lipid hydroperoxides in cells. Vitamin K is known to have antioxidant properties and plays a role in reducing oxidative stress, particularly in lipid cell membranes. Vitamin K reduces the level of reactive oxygen species by modulating the expression of antioxidant enzymes. Additionally, vitamin K decreases inflammation and potentially prevents ferroptosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) is associated with oxidant–antioxidant imbalance. Studies have shown that intensified ferroptosis occurs in various tissues and cells affected by COVID-19. Vitamin K supplementation during SARS-CoV-2 infection may have a positive effect on reducing the severity of the disease. Preliminary research suggests that vitamin K may reduce lipid peroxidation and inhibit ferroptosis, potentially contributing to its therapeutic effects in COVID-19 patients. The links between ferroptosis, vitamin K, and SARS-CoV-2 infection require further investigation, particularly in the context of developing potential treatment strategies for COVID-19. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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30 pages, 3373 KiB  
Review
Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment
by Biancamaria Longoni and Gian Carlo Demontis
Antioxidants 2023, 12(3), 617; https://doi.org/10.3390/antiox12030617 - 02 Mar 2023
Cited by 1 | Viewed by 2654
Abstract
The retina is an oxidative stress-prone tissue due to high content of polyunsaturated lipids, exposure to visible light stimuli in the 400–480 nm range, and high oxygen availability provided by choroidal capillaries to support oxidative metabolism. Indeed, lipids’ peroxidation and their conversion into [...] Read more.
The retina is an oxidative stress-prone tissue due to high content of polyunsaturated lipids, exposure to visible light stimuli in the 400–480 nm range, and high oxygen availability provided by choroidal capillaries to support oxidative metabolism. Indeed, lipids’ peroxidation and their conversion into reactive species promoting inflammation have been reported and connected to retinal degenerations. Here, we review recent evidence showing how retinal polyunsaturated lipids, in addition to oxidative stress and damage, may counteract the inflammatory response triggered by blue light-activated carotenoid derivatives, enabling long-term retina operation despite its prooxidant environment. These two aspects of retinal polyunsaturated lipids require tight control over their synthesis to avoid overcoming their protective actions by an increase in lipid peroxidation due to oxidative stress. We review emerging evidence on different transcriptional control mechanisms operating in retinal cells to modulate polyunsaturated lipid synthesis over the life span, from the immature to the ageing retina. Finally, we discuss the antioxidant role of food nutrients such as xanthophylls and carotenoids that have been shown to empower retinal cells’ antioxidant responses and counteract the adverse impact of prooxidant stimuli on sight. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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20 pages, 1885 KiB  
Review
Antenatal and Postnatal Sequelae of Oxidative Stress in Preterm Infants: A Narrative Review Targeting Pathophysiological Mechanisms
by Silvia Martini, Arianna Aceti, Anna Nunzia Della Gatta, Isadora Beghetti, Concetta Marsico, Gianluigi Pilu and Luigi Corvaglia
Antioxidants 2023, 12(2), 422; https://doi.org/10.3390/antiox12020422 - 09 Feb 2023
Cited by 1 | Viewed by 1784
Abstract
The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as [...] Read more.
The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as OS-related neonatal diseases. Due to the physiological immaturity of their antioxidant defenses and to the enhanced antenatal and postnatal exposure to free radicals, preterm infants are particularly susceptible to oxidative damage, and several pathophysiological cascades involved in the development of prematurity-related complications are tightly related to OS. This narrative review aims to provide a detailed overview of the OS-related pathophysiological mechanisms that contribute to the main OS-related diseases during pregnancy and in the early postnatal period in the preterm population. Particularly, focus has been placed on pregnancy disorders typically associated with iatrogenic or spontaneous preterm birth, such as intrauterine growth restriction, pre-eclampsia, gestational diabetes, chorioamnionitis, and on specific postnatal complications for which the role of OS has been largely ascertained (e.g., respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis). Knowledge of the underlying pathophysiological mechanisms may increase awareness on potential strategies aimed at preventing the development of these conditions or at reducing the ensuing clinical burden. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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17 pages, 2065 KiB  
Review
Pleiotropic Roles of a KEAP1-Associated Deubiquitinase, OTUD1
by Daisuke Oikawa, Kouhei Shimizu and Fuminori Tokunaga
Antioxidants 2023, 12(2), 350; https://doi.org/10.3390/antiox12020350 - 01 Feb 2023
Cited by 4 | Viewed by 2897
Abstract
Protein ubiquitination, which is catalyzed by ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, and ubiquitin ligases, is a crucial post-translational modification to regulate numerous cellular functions in a spatio–temporal-specific manner. The human genome encodes ~100 deubiquitinating enzymes (DUBs), which antagonistically regulate the ubiquitin system. OTUD1, an [...] Read more.
Protein ubiquitination, which is catalyzed by ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, and ubiquitin ligases, is a crucial post-translational modification to regulate numerous cellular functions in a spatio–temporal-specific manner. The human genome encodes ~100 deubiquitinating enzymes (DUBs), which antagonistically regulate the ubiquitin system. OTUD1, an ovarian tumor protease (OTU) family DUB, has an N-terminal-disordered alanine-, proline-, glycine-rich region (APGR), a catalytic OTU domain, and a ubiquitin-interacting motif (UIM). OTUD1 preferentially hydrolyzes lysine-63-linked ubiquitin chains in vitro; however, recent studies indicate that OTUD1 cleaves various ubiquitin linkages, and is involved in the regulation of multiple cellular functions. Thus, OTUD1 predominantly functions as a tumor suppressor by targeting p53, SMAD7, PTEN, AKT, IREB2, YAP, MCL1, and AIF. Furthermore, OTUD1 regulates antiviral signaling, innate and acquired immune responses, and cell death pathways. Similar to Nrf2, OTUD1 contains a KEAP1-binding ETGE motif in its APGR and regulates the reactive oxygen species (ROS)-mediated oxidative stress response and cell death. Importantly, in addition to its association with various cancers, including multiple myeloma, OTUD1 is involved in acute graft-versus-host disease and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis. Thus, OTUD1 is an important DUB as a therapeutic target for a variety of diseases. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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19 pages, 6044 KiB  
Review
Oxidative Stress Modulation by ncRNAs and Their Emerging Role as Therapeutic Targets in Atherosclerosis and Non-Alcoholic Fatty Liver Disease
by Jorge Infante-Menéndez, Paula González-López, Raquel Huertas-Lárez, Almudena Gómez-Hernández and Óscar Escribano
Antioxidants 2023, 12(2), 262; https://doi.org/10.3390/antiox12020262 - 24 Jan 2023
Cited by 1 | Viewed by 1917
Abstract
Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are pathologies related to ectopic fat accumulation, both of which are continuously increasing in prevalence. These threats are prompting researchers to develop effective therapies for their clinical management. One of the common pathophysiological alterations that underlies [...] Read more.
Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are pathologies related to ectopic fat accumulation, both of which are continuously increasing in prevalence. These threats are prompting researchers to develop effective therapies for their clinical management. One of the common pathophysiological alterations that underlies both diseases is oxidative stress (OxS), which appears as a result of lipid deposition in affected tissues. However, the molecular mechanisms that lead to OxS generation are different in each disease. Non-coding RNAs (ncRNAs) are RNA transcripts that do not encode proteins and function by regulating gene expression. In recent years, the involvement of ncRNAs in OxS modulation has become more recognized. This review summarizes the most recent advances regarding ncRNA-mediated regulation of OxS in atherosclerosis and NAFLD. In both diseases, ncRNAs can exert pro-oxidant or antioxidant functions by regulating gene targets and even other ncRNAs, positioning them as potential therapeutic targets. Interestingly, both diseases have common altered ncRNAs, suggesting that the same molecule can be targeted simultaneously when both diseases coexist. Finally, since some ncRNAs have already been used as therapeutic agents, their roles as potential drugs for the clinical management of atherosclerosis and NAFLD are analyzed. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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21 pages, 1770 KiB  
Review
Novel, Innovative Models to Study Ischemia/Reperfusion-Related Redox Damage in Organ Transplantation
by Julia Hofmann, Marlene Pühringer, Sabrina Steinkellner, Aline-Sophie Holl, Andras T. Meszaros, Stefan Schneeberger, Jakob Troppmair and Theresa Hautz
Antioxidants 2023, 12(1), 31; https://doi.org/10.3390/antiox12010031 - 24 Dec 2022
Viewed by 2108
Abstract
The implementation of ex vivo organ machine perfusion (MP) into clinical routine undoubtedly helped to increase the donor pool. It enables not just organ assessment, but potentially regeneration and treatment of marginal organs in the future. During organ procurement, redox-stress triggered ischemia-reperfusion injury [...] Read more.
The implementation of ex vivo organ machine perfusion (MP) into clinical routine undoubtedly helped to increase the donor pool. It enables not just organ assessment, but potentially regeneration and treatment of marginal organs in the future. During organ procurement, redox-stress triggered ischemia-reperfusion injury (IRI) is inevitable, which in addition to pre-existing damage negatively affects such organs. Ex vivo MP enables to study IRI-associated tissue damage and its underlying mechanisms in a near to physiological setting. However, research using whole organs is limited and associated with high costs. Here, in vitro models well suited for early stage research or for studying particular disease mechanisms come into play. While cell lines convince with simplicity, they do not exert all organ-specific functions. Tissue slice cultures retain the three-dimensional anatomical architecture and cells remain within their naïve tissue-matrix configuration. Organoids may provide an even closer modelling of physiologic organ function and spatial orientation. In this review, we discuss the role of oxidative stress during ex vivo MP and the suitability of currently available in vitro models to further study the underlying mechanisms and to pretest potential treatment strategies. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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20 pages, 2500 KiB  
Review
More than Just Antioxidants: Redox-Active Components and Mechanisms Shaping Redox Signalling Network
by Monika Kuczyńska, Patrycja Jakubek and Agnieszka Bartoszek
Antioxidants 2022, 11(12), 2403; https://doi.org/10.3390/antiox11122403 - 04 Dec 2022
Cited by 6 | Viewed by 1849
Abstract
The concept of oxidative stress as a condition underlying a multitude of human diseases has led to immense interest in the search for antioxidant-based remedies. The simple and intuitive story of “the bad” reactive oxygen species (ROS) and “the good” antioxidants quickly (and [...] Read more.
The concept of oxidative stress as a condition underlying a multitude of human diseases has led to immense interest in the search for antioxidant-based remedies. The simple and intuitive story of “the bad” reactive oxygen species (ROS) and “the good” antioxidants quickly (and unsurprisingly) lead to the commercial success of products tagged “beneficial to health” based solely on the presence of antioxidants. The commercial success of antioxidants by far preceded the research aimed at understanding the exact redox-related mechanisms that are in control of shaping the states of health and disease. This review describes the redox network formed by the interplay of ROS with cellular molecules and the resulting regulation of processes at the genomic and proteomic levels. Key players of this network are presented, both involved in redox signalling and control of cellular metabolism linked to most, if not all, physiological processes. In particular, this review focuses on the concept of reductive stress, which still remains less well-established compared to oxidative stress. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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17 pages, 1040 KiB  
Review
Antioxidant Supplementation in Oxidative Stress-Related Diseases: What Have We Learned from Studies on Alpha-Tocopherol?
by Fleur L. Meulmeester, Jiao Luo, Leon G. Martens, Kevin Mills, Diana van Heemst and Raymond Noordam
Antioxidants 2022, 11(12), 2322; https://doi.org/10.3390/antiox11122322 - 24 Nov 2022
Cited by 16 | Viewed by 3267
Abstract
Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense [...] Read more.
Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (α-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on α-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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26 pages, 2039 KiB  
Review
On the Potential Role of the Antioxidant Couple Vitamin E/Selenium Taken by the Oral Route in Skin and Hair Health
by Joël Pincemail and Smail Meziane
Antioxidants 2022, 11(11), 2270; https://doi.org/10.3390/antiox11112270 - 17 Nov 2022
Cited by 10 | Viewed by 7311
Abstract
The relationship between oxidative stress and skin aging/disorders is well established. Many topical and oral antioxidants (vitamins C and E, carotenoids, polyphenols) have been proposed to protect the skin against the deleterious effect induced by increased reactive oxygen species production, particularly in the [...] Read more.
The relationship between oxidative stress and skin aging/disorders is well established. Many topical and oral antioxidants (vitamins C and E, carotenoids, polyphenols) have been proposed to protect the skin against the deleterious effect induced by increased reactive oxygen species production, particularly in the context of sun exposure. In this review, we focused on the combination of vitamin E and selenium taken in supplements since both molecules act in synergy either by non-enzymatic and enzymatic pathways to eliminate skin lipids peroxides, which are strongly implicated in skin and hair disorders. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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26 pages, 1949 KiB  
Review
The Role of the Thioredoxin System in Brain Diseases
by Geir Bjørklund, Lili Zou, Massimiliano Peana, Christos T. Chasapis, Tony Hangan, Jun Lu and Michael Maes
Antioxidants 2022, 11(11), 2161; https://doi.org/10.3390/antiox11112161 - 31 Oct 2022
Cited by 16 | Viewed by 3258
Abstract
The thioredoxin system, consisting of thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH, plays a fundamental role in the control of antioxidant defenses, cell proliferation, redox states, and apoptosis. Aberrations in the Trx system may lead to increased oxidative stress toxicity and neurodegenerative processes. [...] Read more.
The thioredoxin system, consisting of thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH, plays a fundamental role in the control of antioxidant defenses, cell proliferation, redox states, and apoptosis. Aberrations in the Trx system may lead to increased oxidative stress toxicity and neurodegenerative processes. This study reviews the role of the Trx system in the pathophysiology and treatment of Alzheimer’s, Parkinson’s and Huntington’s diseases, brain stroke, and multiple sclerosis. Trx system plays an important role in the pathophysiology of those disorders via multiple interactions through oxidative stress, apoptotic, neuro-immune, and pro-survival pathways. Multiple aberrations in Trx and TrxR systems related to other redox systems and their multiple reciprocal relationships with the neurodegenerative, neuro-inflammatory, and neuro-oxidative pathways are here analyzed. Genetic and environmental factors (nutrition, metals, and toxins) may impact the function of the Trx system, thereby contributing to neuropsychiatric disease. Aberrations in the Trx and TrxR systems could be a promising drug target to prevent and treat neurodegenerative, neuro-inflammatory, neuro-oxidative stress processes, and related brain disorders. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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28 pages, 797 KiB  
Review
Vitamin D3 and Ischemic Stroke: A Narrative Review
by Władysław Lasoń, Danuta Jantas, Monika Leśkiewicz, Magdalena Regulska and Agnieszka Basta-Kaim
Antioxidants 2022, 11(11), 2120; https://doi.org/10.3390/antiox11112120 - 27 Oct 2022
Cited by 9 | Viewed by 5158
Abstract
Ischemic stroke is one of the major causes of death and permanent disability worldwide. The only efficient treatment to date is anticoagulant therapy and thrombectomy, which enable restitution of blood flow to ischemic tissues. Numerous promising neuroprotectants have failed in clinical trials. Given [...] Read more.
Ischemic stroke is one of the major causes of death and permanent disability worldwide. The only efficient treatment to date is anticoagulant therapy and thrombectomy, which enable restitution of blood flow to ischemic tissues. Numerous promising neuroprotectants have failed in clinical trials. Given the complex pathomechanism of stroke, a multitarget pharmacotherapy seems a more rational approach in stroke prevention and treatment than drugs acting on single molecular targets. Recently, vitamin D3 has emerged as a potential treatment adjunct for ischemic stroke, as it interferes with the key prosurvival pathways and shows neuroprotective, anti-inflammatory, regenerative and anti-aging properties in both neuronal and vascular tissue. Moreover, the stimulatory effect of vitamin D3 on brain-derived neurotrophic factor (BDNF) signaling and neuroplasticity may play a role not only in the recovery of neurological functions, but also in ameliorating post-stroke depression and anxiety. This narrative review presents advances in research on the biochemical mechanisms of stroke-related brain damage, and the genomic and non-genomic effects of vitamin D3 which may interfere with diverse cell death signaling pathways. Next, we discuss the results of in vitro and in vivo experimental studies on the neuroprotective potential of 1alpha,25-dihydroxyvitamin D3 (calcitriol) in brain ischemia models. Finally, the outcomes of clinical trials on vitamin D3 efficiency in ischemic stroke patients are briefly reviewed. Despite the mixed results of the clinical trials, it appears that vitamin D3 still holds promise in preventing or ameliorating neurological and psychiatric consequences of ischemic stroke and certainly deserves further study. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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38 pages, 2791 KiB  
Review
Natural Active Ingredients for Poly (Lactic Acid)-Based Materials: State of the Art and Perspectives
by Andrea Lombardi, Andrea Fochetti, Pamela Vignolini, Margherita Campo, Alessandra Durazzo, Massimo Lucarini, Debora Puglia, Francesca Luzi, Marco Papalini, Monia Renzi, Andrea Cavallo and Roberta Bernini
Antioxidants 2022, 11(10), 2074; https://doi.org/10.3390/antiox11102074 - 20 Oct 2022
Cited by 5 | Viewed by 2740
Abstract
This review describes the state of the art in the field of poly (lactic acid) (PLA)-based materials activated by natural compounds and extracts (active ingredients, AIs) from plant sources for food and biomedical applications. With a multidisciplinary approach, after a description of the [...] Read more.
This review describes the state of the art in the field of poly (lactic acid) (PLA)-based materials activated by natural compounds and extracts (active ingredients, AIs) from plant sources for food and biomedical applications. With a multidisciplinary approach, after a description of the synthesis and properties of PLA, special attention was paid to the chemical properties and unconventional extraction technologies of AIs used for PLA activation. Innovative techniques for the incorporation of AIs into PLA; characterization and the antioxidant and antimicrobial properties of the novel materials were discussed. In view of future perspectives, this study has evidenced that some aspects need to be further investigated from joint research between academia and industry, according to the green chemistry principles and circular economy strategy. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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12 pages, 641 KiB  
Review
Anti- and Pro-Oxidant Properties of Essential Oils against Antimicrobial Resistance
by Amanda Shen-Yee Kong, Sathiya Maran, Polly Soo-Xi Yap, Swee-Hua Erin Lim, Shun-Kai Yang, Wan-Hee Cheng, Yong-Hui Tan and Kok-Song Lai
Antioxidants 2022, 11(9), 1819; https://doi.org/10.3390/antiox11091819 - 15 Sep 2022
Cited by 9 | Viewed by 2434
Abstract
The rapid evolution of antimicrobial resistance (AMR) has remained a major public health issue, reducing the efficacy of antibiotics and increasing the difficulty of treating infections. The discovery of novel antimicrobial agents is urgently needed to overcome the challenges created by AMR. Natural [...] Read more.
The rapid evolution of antimicrobial resistance (AMR) has remained a major public health issue, reducing the efficacy of antibiotics and increasing the difficulty of treating infections. The discovery of novel antimicrobial agents is urgently needed to overcome the challenges created by AMR. Natural products such as plant extracts and essential oils (EOs) have been viewed as potential candidates to combat AMR due to their complex chemistry that carries inherent pro-oxidant and antioxidant properties. EOs and their constituents that hold pro-oxidant properties can induce oxidative stress by producing reactive oxygen species (ROS), leading to biological damage in target cells. In contrast, the antioxidant properties scavenge free radicals through offsetting ROS. Both pro-oxidant and antioxidant activities in EOs represent a promising strategy to tackle AMR. Thus, this review aimed to discuss how pro-oxidants and antioxidants in EOs may contribute to the mitigation of AMR and provided a detailed description of the challenges and limitations of utilizing them as a means to combat AMR. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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21 pages, 747 KiB  
Review
Antioxidant Effects of Dietary Supplements on Adult COVID-19 Patients: Why Do We Not Also Use Them in Children?
by Veronica Notarbartolo, Claudio Montante, Giuliana Ferrante and Mario Giuffrè
Antioxidants 2022, 11(9), 1638; https://doi.org/10.3390/antiox11091638 - 24 Aug 2022
Cited by 1 | Viewed by 2633
Abstract
Respiratory tract infections (RTIs) are very common in children, especially in the first five years of life, and several viruses, such as the influenza virus, Respiratory Syncytial Virus, and Rhinovirus, are triggers for symptoms that usually affect the upper airways. It has been [...] Read more.
Respiratory tract infections (RTIs) are very common in children, especially in the first five years of life, and several viruses, such as the influenza virus, Respiratory Syncytial Virus, and Rhinovirus, are triggers for symptoms that usually affect the upper airways. It has been known that during respiratory viral infections, a condition of oxidative stress (OS) occurs, and many studies have suggested the potential use of antioxidants as complementary components in prophylaxis and/or therapy of respiratory viral infections. Preliminary data have demonstrated that antioxidants may also interfere with the new coronavirus 2’s entry and replication in human cells, and that they have a role in the downregulation of several pathogenetic mechanisms involved in disease severity. Starting from preclinical data, the aim of this narrative review is to evaluate the current evidence about the main antioxidants that are potentially useful for preventing and treating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in adults and to speculate on their possible use in children by exploring the most relevant issues affecting their use in clinical practice, as well as the associated evidence gaps and research limitations. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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23 pages, 1279 KiB  
Review
Role of Oxidative Stress and Antioxidants in Acquired Inner Ear Disorders
by Megumi Kishimoto-Urata, Shinji Urata, Chisato Fujimoto and Tatsuya Yamasoba
Antioxidants 2022, 11(8), 1469; https://doi.org/10.3390/antiox11081469 - 27 Jul 2022
Cited by 17 | Viewed by 3823
Abstract
Oxygen metabolism in the mitochondria is essential for biological activity, and reactive oxygen species (ROS) are produced simultaneously in the cell. Once an imbalance between ROS production and degradation (oxidative stress) occurs, cells are damaged. Sensory organs, especially those for hearing, are constantly [...] Read more.
Oxygen metabolism in the mitochondria is essential for biological activity, and reactive oxygen species (ROS) are produced simultaneously in the cell. Once an imbalance between ROS production and degradation (oxidative stress) occurs, cells are damaged. Sensory organs, especially those for hearing, are constantly exposed during daily life. Therefore, almost all mammalian species are liable to hearing loss depending on their environment. In the auditory pathway, hair cells, spiral ganglion cells, and the stria vascularis, where mitochondria are abundant, are the main targets of ROS. Excessive generation of ROS in auditory sensory organs is widely known to cause sensorineural hearing loss, and mitochondria-targeted antioxidants are candidates for treatment. This review focuses on the relationship between acquired hearing loss and antioxidant use to provide an overview of novel antioxidants, namely medicines, supplemental nutrients, and natural foods, based on clinical, animal, and cultured-cell studies. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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13 pages, 2809 KiB  
Review
Molecular Properties of β-Carotene Oxygenases and Their Potential in Industrial Production of Vitamin A and Its Derivatives
by Kyung-Chul Shin, Min-Ju Seo, Yeong-Su Kim and Soo-Jin Yeom
Antioxidants 2022, 11(6), 1180; https://doi.org/10.3390/antiox11061180 - 16 Jun 2022
Cited by 1 | Viewed by 3951
Abstract
β-Carotene 15,15′-oxygenase (BCO1) and β-carotene 9′,10′-oxygenase (BCO2) are potential producers of vitamin A derivatives, since they can catalyze the oxidative cleavage of dietary provitamin A carotenoids to retinoids and derivative such as apocarotenal. Retinoids are a class of chemical compounds that are vitamers [...] Read more.
β-Carotene 15,15′-oxygenase (BCO1) and β-carotene 9′,10′-oxygenase (BCO2) are potential producers of vitamin A derivatives, since they can catalyze the oxidative cleavage of dietary provitamin A carotenoids to retinoids and derivative such as apocarotenal. Retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it, and are essential nutrients for humans and highly valuable in the food and cosmetics industries. β-carotene oxygenases (BCOs) from various organisms have been overexpressed in heterogeneous bacteria, such as Escherichia coli, and their biochemical properties have been studied. For the industrial production of retinal, there is a need for increased production of a retinal producer and biosynthesis of retinal using biocatalyst systems improved by enzyme engineering. The current review aims to discuss BCOs from animal, plants, and bacteria, and to elaborate on the recent progress in our understanding of their functions, biochemical properties, substrate specificity, and enzyme activities with respect to the production of retinoids in whole-cell conditions. Moreover, we specifically propose ways to integrate BCOs into retinal biosynthetic bacterial systems to improve the performance of retinal production. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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16 pages, 627 KiB  
Review
Anti-Oxidative Therapy in Islet Cell Transplantation
by Natsuki Eguchi, Kimia Damyar, Michael Alexander, Donald Dafoe, Jonathan R. T. Lakey and Hirohito Ichii
Antioxidants 2022, 11(6), 1038; https://doi.org/10.3390/antiox11061038 - 24 May 2022
Cited by 7 | Viewed by 2104
Abstract
Islet cell transplantation has become a favorable therapeutic approach in the treatment of Type 1 Diabetes due to the lower surgical risks and potential complications compared to conventional pancreas transplantation. Despite significant improvements in islet cell transplantation outcomes, several limitations hamper long-term graft [...] Read more.
Islet cell transplantation has become a favorable therapeutic approach in the treatment of Type 1 Diabetes due to the lower surgical risks and potential complications compared to conventional pancreas transplantation. Despite significant improvements in islet cell transplantation outcomes, several limitations hamper long-term graft survival due to tremendous damage and loss of islet cells during the islet cell transplantation process. Oxidative stress has been identified as an omnipresent stressor that negatively affects both the viability and function of isolated islets. Furthermore, it has been established that at baseline, pancreatic β cells exhibit reduced antioxidative capacity, rendering them even more susceptible to oxidative stress during metabolic stress. Thus, identifying antioxidants capable of conferring protection against oxidative stressors present throughout the islet transplantation process is a valuable approach to improving the overall outcomes of islet cell transplantation. In this review we discuss the potential application of antioxidative therapy during each step of islet cell transplantation. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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15 pages, 1164 KiB  
Review
Mitochondrial ROS, ER Stress, and Nrf2 Crosstalk in the Regulation of Mitochondrial Apoptosis Induced by Arsenite
by Orazio Cantoni, Ester Zito, Andrea Guidarelli, Mara Fiorani and Pietro Ghezzi
Antioxidants 2022, 11(5), 1034; https://doi.org/10.3390/antiox11051034 - 23 May 2022
Cited by 13 | Viewed by 3616
Abstract
Long-term ingestion of arsenicals, a heterogeneous group of toxic compounds, has been associated with a wide spectrum of human pathologies, which include various malignancies. Although their mechanism of toxicity remains largely unknown, it is generally believed that arsenicals mainly produce their effects via [...] Read more.
Long-term ingestion of arsenicals, a heterogeneous group of toxic compounds, has been associated with a wide spectrum of human pathologies, which include various malignancies. Although their mechanism of toxicity remains largely unknown, it is generally believed that arsenicals mainly produce their effects via direct binding to protein thiols and ROS formation in different subcellular compartments. The generality of these mechanisms most probably accounts for the different effects mediated by different forms of the metalloid in a variety of cells and tissues. In order to learn more about the molecular mechanisms of cyto- and genotoxicity, there is a need to focus on specific arsenic compounds under tightly controlled conditions. This review focuses on the mechanisms regulating the mitochondrial formation of ROS after exposure to low concentrations of a specific arsenic compound, NaAsO2, and their crosstalk with the nuclear factor (erythroid-2 related) factor 2 antioxidant signaling and the endoplasmic reticulum stress response. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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22 pages, 1165 KiB  
Review
New Progress in the Molecular Regulations and Therapeutic Applications in Cardiac Oxidative Damage Caused by Pressure Overload
by Xiaomeng Shi, Arin Dorsey and Hongyu Qiu
Antioxidants 2022, 11(5), 877; https://doi.org/10.3390/antiox11050877 - 29 Apr 2022
Cited by 2 | Viewed by 2282
Abstract
Chronic pressure overload is a key risk factor for mortality due to its subsequent development of heart failure, in which the underlying molecular mechanisms remain vastly undetermined. In this review, we updated the latest advancements for investigating the role and relevant mechanisms of [...] Read more.
Chronic pressure overload is a key risk factor for mortality due to its subsequent development of heart failure, in which the underlying molecular mechanisms remain vastly undetermined. In this review, we updated the latest advancements for investigating the role and relevant mechanisms of oxidative stress involved in the pathogenesis of pressure-overload-induced cardiomyopathy and cardiac dysfunction, focusing on significant biological sources of reactive oxygen species (free radical) production, antioxidant defenses, and their association with the cardiac metabolic remodeling in the stressed heart. We also summarize the newly developed preclinical therapeutic approaches in animal models for pressure-overload-induced myocardial damage. This review aims to enhance the current understanding of the mechanisms of chronic hypertensive heart failure and potentially improve the development of better therapeutic strategies for the associated diseases. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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30 pages, 1962 KiB  
Review
Superoxide Radicals in the Execution of Cell Death
by Junichi Fujii, Takujiro Homma and Tsukasa Osaki
Antioxidants 2022, 11(3), 501; https://doi.org/10.3390/antiox11030501 - 04 Mar 2022
Cited by 86 | Viewed by 11559
Abstract
Superoxide is a primary oxygen radical that is produced when an oxygen molecule receives one electron. Superoxide dismutase (SOD) plays a primary role in the cellular defense against an oxidative insult by ROS. However, the resulting hydrogen peroxide is still reactive and, in [...] Read more.
Superoxide is a primary oxygen radical that is produced when an oxygen molecule receives one electron. Superoxide dismutase (SOD) plays a primary role in the cellular defense against an oxidative insult by ROS. However, the resulting hydrogen peroxide is still reactive and, in the presence of free ferrous iron, may produce hydroxyl radicals and exacerbate diseases. Polyunsaturated fatty acids are the preferred target of hydroxyl radicals. Ferroptosis, a type of necrotic cell death induced by lipid peroxides in the presence of free iron, has attracted considerable interest because of its role in the pathogenesis of many diseases. Radical electrons, namely those released from mitochondrial electron transfer complexes, and those produced by enzymatic reactions, such as lipoxygenases, appear to cause lipid peroxidation. While GPX4 is the most potent anti-ferroptotic enzyme that is known to reduce lipid peroxides to alcohols, other antioxidative enzymes are also indirectly involved in protection against ferroptosis. Moreover, several low molecular weight compounds that include α-tocopherol, ascorbate, and nitric oxide also efficiently neutralize radical electrons, thereby suppressing ferroptosis. The removal of radical electrons in the early stages is of primary importance in protecting against ferroptosis and other diseases that are related to oxidative stress. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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8 pages, 610 KiB  
Opinion
Oxidants and Cardiorenal Vascular Remodeling—Insights from Rare Genetic Tubulopathies: Bartter’s and Gitelman’s Syndromes
by Luca Sgarabotto, Verdiana Ravarotto, Lucia Federica Stefanelli, Martina Cacciapuoti, Paul A. Davis, Federico Nalesso and Lorenzo A. Calò
Antioxidants 2023, 12(4), 811; https://doi.org/10.3390/antiox12040811 - 26 Mar 2023
Cited by 1 | Viewed by 1287
Abstract
Two human genetic tubulopathies, Bartter’s (BS) and Gitelman’s (GS) syndromes, have normo/hypotension and absent cardiac remodeling despite their apparent angiotensin system (RAS) activation. This seeming contradiction has led to an extensive investigation of BSGS patients, the result of which is that BSGS represents [...] Read more.
Two human genetic tubulopathies, Bartter’s (BS) and Gitelman’s (GS) syndromes, have normo/hypotension and absent cardiac remodeling despite their apparent angiotensin system (RAS) activation. This seeming contradiction has led to an extensive investigation of BSGS patients, the result of which is that BSGS represents a mirror image of hypertension. BSGS’s unique set of properties has then permitted their use as a human model to probe and characterize RAS system pathways and oxidative stress in cardiovascular and renal remodeling and pathophysiology. This review details the results using GSBS patients that provide a deeper understanding of Ang II signaling and its associated oxidants/oxidative stress in humans. By providing a more complete and complex picture of cardiovascular and renal remodeling pathways and processes, studies of GSBS can inform the identification and selection of new targets and therapies to treat these and other oxidant-related disorders. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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7 pages, 1096 KiB  
Perspective
Potential Impacts of Hydralazine as a Novel Antioxidant on Cardiovascular and Renal Disease—Beyond Vasodilation and Blood Pressure Lowering
by Ting-Ting Chang and Jaw-Wen Chen
Antioxidants 2022, 11(11), 2224; https://doi.org/10.3390/antiox11112224 - 11 Nov 2022
Cited by 4 | Viewed by 3926
Abstract
Hydralazine is a traditional antihypertensive drug that was developed several decades ago. Its most well-known effect is blood pressure lowering by arterial vasodilation. While mainly used an adjunct treatment for clinical hypertension or chronic heart failure, this old drug has also shown potential [...] Read more.
Hydralazine is a traditional antihypertensive drug that was developed several decades ago. Its most well-known effect is blood pressure lowering by arterial vasodilation. While mainly used an adjunct treatment for clinical hypertension or chronic heart failure, this old drug has also shown potential as a repurposing drug for the atherosclerosis vascular disease and various kidney diseases. Recent experimental studies suggest that hydralazine exerts antioxidative, anti-apoptotic, and HIF-1α stabilization effects for angiogenesis and vascular protection. Hydralazine also exerts reno-protective effects via its antioxidation, DNA demethylation, and anti-inflammation abilities. The above evidence provides advanced rationales for new applications of this drug beyond blood pressure lowering and arterial vasodilation. Here, we summarized the recent experimental advances in the use of hydralazine for either a vascular disease or kidney diseases, or both. Given the wide populations of people with cardiovascular and/or kidney diseases, future studies are worth validating the potential impacts of hydralazine on the clinical outcomes in selected patients. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)
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