Antioxidants

25 pages, 10517 KiB

Open AccessArticle

Glutathione and Ascorbic Acid Accumulation in Mango Pulp Under Enhanced UV-B Based on Transcriptome

by Hassam Tahir, Muhammad Sajjad, Minjie Qian, Muhammad Zeeshan Ul Haq, Ashar Tahir, Muhammad Aamir Farooq, Ling Wei, Shaopu Shi, Kaibing Zhou and Quansheng Yao

Antioxidants 2024, 13(11), 1429; https://doi.org/10.3390/antiox13111429 - 20 Nov 2024

Viewed by 221

Abstract

Mango (Mangifera indica), a nutritionally rich tropical fruit, is significantly impacted by UV-B radiation, which induces oxidative stress and disrupts physiological processes. This study aimed to investigate mango pulp’s molecular and biochemical responses to UV-B stress (96 kJ/mol) from the unripe [...] Read more.

Mango (Mangifera indica), a nutritionally rich tropical fruit, is significantly impacted by UV-B radiation, which induces oxidative stress and disrupts physiological processes. This study aimed to investigate mango pulp’s molecular and biochemical responses to UV-B stress (96 kJ/mol) from the unripe to mature stages over three consecutive years, with samples collected at 10-day intervals. UV-B stress affected both non-enzymatic parameters, such as maturity index, reactive oxygen species (ROS) levels, membrane permeability, and key enzymatic components of the ascorbate-glutathione (AsA-GSH) cycle. These enzymes included glutathione reductase (GR), gamma-glutamyl transferase (GGT), glutathione S-transferases (GST), glutathione peroxidase (GPX), glucose-6-phosphate dehydrogenase (G6PDH), galactono-1,4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX), ascorbate oxidase (AAO), and monodehydroascorbate reductase (MDHAR). Transcriptomic analysis revealed 18 differentially expressed genes (DEGs) related to the AsA-GSH cycle, including MiGR, MiGGT1, MiGGT2, MiGPX1, MiGPX2, MiGST1, MiGST2, MiGST3, MiG6PDH1, MiG6PDH2, MiGalLDH, MiAPX1, MiAPX2, MiAAO1, MiAAO2, MiAAO3, MiAAO4, and MiMDHAR, validated through qRT-PCR. The findings suggest that UV-B stress activates a complex regulatory network in mango pulp to optimize ROS detoxification and conserve antioxidants, offering insights for enhancing the resilience of tropical fruit trees to environmental stressors. Full article

(This article belongs to the Special Issue Non-Enzymatic Antioxidant Molecules and Their Defense Mechanisms)

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30 pages, 2905 KiB

Open AccessArticle

(Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells

by Linda M. Bakker, Michael E. Boulton and Małgorzata B. Różanowska

Antioxidants 2024, 13(11), 1428; https://doi.org/10.3390/antiox13111428 - 20 Nov 2024

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Abstract

Docosahexaenoate is a cytoprotective ω-3 polyunsaturated lipid that is abundant in the retina and is essential for its function. Due to its six unsaturated double bonds, docosahexaenoate is highly susceptible to oxidation and the formation of products with photosensitizing properties. This study aimed [...] Read more.

Docosahexaenoate is a cytoprotective ω-3 polyunsaturated lipid that is abundant in the retina and is essential for its function. Due to its six unsaturated double bonds, docosahexaenoate is highly susceptible to oxidation and the formation of products with photosensitizing properties. This study aimed to test on cultured human retinal pigment epithelial cells ARPE-19 the (photo)cytotoxic potential of partly oxidized docosahexaenoate and its effect on the formation of lipofuscin from phagocytosed photoreceptor outer segments (POSs). The results demonstrate that the cytoprotective effects of docosahexaenoate do not counteract the deleterious effects of its oxidation products, leading to the concentration-dependent loss of cell metabolic activity, which is exacerbated by concomitant exposure to visible light. Partly oxidized docosahexaenoate does not cause permeability of the cell plasma membrane but does cause apoptosis. While vitamin E can provide partial protection from the (photo)toxicity of partly oxidized docosahexaenoate, zeaxanthin undergoes rapid photodegradation and can exacerbate the (photo)toxicity. Feeding cells with POSs enriched in partly oxidized docosahexaenoate results in a greater accumulation of intracellular fluorescent lipofuscin than in cells fed POSs without the addition. In conclusion, partly oxidized docosahexaenoate increases the accumulation of lipofuscin-like intracellular deposits, is cytotoxic, and its toxicity increases during exposure to light. These effects may contribute to the increased progression of geographic atrophy observed after long-term supplementation with docosahexaenoate in age-related macular degeneration patients. Full article

(This article belongs to the Special Issue Antioxidants and Retinal Diseases—2nd Edition)

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21 pages, 3910 KiB

Open AccessArticle

Hit Identification and Functional Validation of Novel Dual Inhibitors of HDAC8 and Tubulin Identified by Combining Docking and Molecular Dynamics Simulations

by Antonio Curcio, Roberta Rocca, Federica Chiera, Maria Eugenia Gallo Cantafio, Ilenia Valentino, Ludovica Ganino, Pierpaolo Murfone, Angela De Simone, Giulia Di Napoli, Stefano Alcaro, Nicola Amodio and Anna Artese

Antioxidants 2024, 13(11), 1427; https://doi.org/10.3390/antiox13111427 - 20 Nov 2024

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Abstract

Chromatin organization, which is under the control of histone deacetylases (HDACs), is frequently deregulated in cancer cells. Amongst HDACs, HDAC8 plays an oncogenic role in different neoplasias by acting on both histone and non-histone substrates. Promising anti-cancer strategies have exploited dual-targeting drugs that [...] Read more.

Chromatin organization, which is under the control of histone deacetylases (HDACs), is frequently deregulated in cancer cells. Amongst HDACs, HDAC8 plays an oncogenic role in different neoplasias by acting on both histone and non-histone substrates. Promising anti-cancer strategies have exploited dual-targeting drugs that inhibit both HDAC8 and tubulin. These drugs have shown the potential to enhance the outcome of anti-cancer treatments by simultaneously targeting multiple pathways critical to disease onset and progression. In this study, a structure-based virtual screening (SBVS) of 96403 natural compounds was performed towards the four Class I HDAC isoforms and tubulin. Using molecular docking and molecular dynamics simulations (MDs), we identified two molecules that could selectively interact with HDAC8 and tubulin. CNP0112925 (arundinin), bearing a polyphenolic structure, was confirmed to inhibit HDAC8 activity and tubulin organization, affecting breast cancer cell viability and triggering mitochondrial superoxide production and apoptosis. Full article

(This article belongs to the Special Issue Multi-Target Profile of Antioxidant Compounds, including Repurposing and Combination Strategies)

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20 pages, 5160 KiB

Open AccessArticle

25-Hydroxycholecalciferol Improves Cardiac Metabolic Adaption, Mitochondrial Biogenetics, and Redox Status to Ameliorate Pathological Remodeling and Functional Failure in Obese Chickens

by Shih-Kai Chiang, Mei-Ying Sin, Jun-Wen Lin, Maraddin Siregar, Gilmour Valdez, Yu-Hui Chen, Thau Kiong Chung, Rosemary L. Walzem, Lin-Chu Chang and Shuen-Ei Chen

Antioxidants 2024, 13(11), 1426; https://doi.org/10.3390/antiox13111426 - 20 Nov 2024

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Abstract

Broiler breeder hens allowed ad libitum (Ad) feed intake developed obesity and cardiac pathogenesis and thereby were susceptible to sudden death. A supplement of 69 µg 25-hydroxycholecalciferol (25-OH-D3)/kg feed rescued the livability of feed-restricted (R) and Ad-hens (mortality; 6.7% vs. 8.9% and 31.1% [...] Read more.

Broiler breeder hens allowed ad libitum (Ad) feed intake developed obesity and cardiac pathogenesis and thereby were susceptible to sudden death. A supplement of 69 µg 25-hydroxycholecalciferol (25-OH-D3)/kg feed rescued the livability of feed-restricted (R) and Ad-hens (mortality; 6.7% vs. 8.9% and 31.1% vs. 48.9%). Necropsy with the surviving counterparts along the time course confirmed alleviation of myocardial remodeling and functional failure by 25-OH-D3, as shown by BNP and MHC-β expressions, pathological hypertrophy, and cardiorespiratory responses (p < 0.05). 25-OH-D3 mitigated cardiac deficient bioenergetics in Ad-hens by rescuing PGC-1α activation, mitochondrial biogenesis, dynamics, and electron transport chain complex activities, and metabolic adaptions in glucose oxidation, pyruvate/lactate interconversion, TCA cycle, and β-oxidation, as well as in TG and ceramide accumulation to limit lipotoxic development (p < 0.05). Supplemental 25-OH-D3 also sustained Nrf2 activation and relieved MDA accumulation, protein carbonylation, and GSH depletion to potentiate cell survival in the failing heart (p < 0.05). Parts of the redox amendments were mediated via lessened blood hematocrit and heme metabolism, and improved iron status and related gene regulations (p < 0.05). In conclusion, 25-OH-D3 ameliorates cardiac pathological remodeling and functional compromise to rescue the livability of obese hens through metabolic flexibility and mitochondrial bioenergetics, and by operating at antioxidant defense, and heme and iron metabolism, to maintain redox homeostasis and sustain cell viability. Full article

(This article belongs to the Special Issue Redox Homeostasis in Poultry/Animal Production)

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22 pages, 6980 KiB

Open AccessReview

The Potential of Plant Extracts Used in Cosmetic Product Applications—Antioxidants Delivery and Mechanism of Actions

by Cristina-Ştefania Gǎlbǎu, Marius Irimie, Andrea Elena Neculau, Lorena Dima, Lea Pogačnik da Silva, Mihai Vârciu and Mihaela Badea

Antioxidants 2024, 13(11), 1425; https://doi.org/10.3390/antiox13111425 - 20 Nov 2024

Viewed by 365

Abstract

Natural ingredients have been used in skincare products for thousands of years. The current focus is on novel natural bioactivities that shield the skin from UV rays and free radicals, among other damaging elements, while enhancing skin health. Free radicals significantly contribute to [...] Read more.

Natural ingredients have been used in skincare products for thousands of years. The current focus is on novel natural bioactivities that shield the skin from UV rays and free radicals, among other damaging elements, while enhancing skin health. Free radicals significantly contribute to skin damage and hasten ageing by interfering with defence and restorative processes. Plants contain natural chemicals that can scavenge free radicals and have antioxidant capabilities. Plant materials are becoming increasingly popular as natural antioxidants related to the expanding interest in plant chemistry. This review focuses on the significance of medicinal plants in skin health and ageing and their potential as a source of antioxidant substances such as vitamins, polyphenols, stilbenes, flavonoids, and methylxanthines. Full article

(This article belongs to the Special Issue Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants—2nd Edition)

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11 pages, 4447 KiB

Open AccessArticle

Low-Dose Melittin Enhanced Pigment Production Through the Upregulation of Tyrosinase Activity and Dendricity in Melanocytes by Limiting Oxidative Stress: A Therapeutic Implication for Vitiligo

by Manoj Kumar Tembhre and Shipra

Antioxidants 2024, 13(11), 1424; https://doi.org/10.3390/antiox13111424 - 20 Nov 2024

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Abstract

Melittin is a major active ingredient of the bee venom produced by honeybees (Apis mellifera) that exerts various biological effects, such as anti-inflammatory, anti-tumor, anti-microbial, and antioxidant. The role of melittin in modulating melanin production by melanocytes is not known. Therefore, [...] Read more.

Melittin is a major active ingredient of the bee venom produced by honeybees (Apis mellifera) that exerts various biological effects, such as anti-inflammatory, anti-tumor, anti-microbial, and antioxidant. The role of melittin in modulating melanin production by melanocytes is not known. Therefore, the present study aimed to study the effect of melittin on melanin production by human melanocytes along with its antioxidant status. Cultured human melanocytes were treated with melittin in a dose- and time-dependent manner, followed by the study of the cell viability, cell proliferation, and total melanin content. The effects of melittin in combination with narrow-band ultraviolet B (NB-UVB) on the total melanin content, melanocyte dendricity, oxidative stress, and the expression of genes associated with melanogenesis were investigated. An increased melanin content was observed with a low dose of melittin (LDM) (alone or in combination with NB-UVB), and there was a corresponding increase in the tyrosinase activity, melanocyte dendricity, and melanogenesis-associated genes. The present study concluded that LDM alone or LDM (+NB-UVB) can induce melanin synthesis by increasing the tyrosinase activity in melanocytes by limiting the oxidative stress, and this may be therapeutically exploited as an adjuvant therapy for vitiligo. Full article

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17 pages, 3000 KiB

Open AccessArticle

PTSD Increases Risk for Hypertension Development Through PVN Activation and Vascular Dysfunction in Sprague Dawley Rats

by Xinqian Chen, Xin Yan, Chunxiu Yu, Qing-hui Chen, Lanrong Bi and Zhiying Shan

Antioxidants 2024, 13(11), 1423; https://doi.org/10.3390/antiox13111423 - 20 Nov 2024

Viewed by 235

Abstract

This study investigates the impact of single prolonged stress (SPS), a model of post-traumatic stress disorder (PTSD), on cardiovascular responses, hypothalamic paraventricular nucleus (PVN) activity, and vascular function to elucidate the mechanisms linking traumatic stress to hypertension. Although SPS did not directly cause [...] Read more.

This study investigates the impact of single prolonged stress (SPS), a model of post-traumatic stress disorder (PTSD), on cardiovascular responses, hypothalamic paraventricular nucleus (PVN) activity, and vascular function to elucidate the mechanisms linking traumatic stress to hypertension. Although SPS did not directly cause chronic hypertension in male Sprague Dawley (SD) rats, it induced acute but transient increases in blood pressure and heart rate and significantly altered the expression of hypertension-associated genes, such as vasopressin, angiotensin II type 1 receptor (AT1R), and FOSL1 in the PVN. Notably, mitochondrial reactive oxygen species (mtROS) were predominantly elevated in the pre-autonomic regions of the PVN, colocalizing with AT1R- and FOSL1-expressing cells, suggesting that oxidative stress may amplify sympathetic activation and stress responses. SPS also increased mRNA levels of pro-inflammatory cytokines (TNFα and IL1β) and inducible nitric oxide synthase (iNOS) in the aorta, and impaired vascular reactivity to vasoconstrictor and vasodilator stimuli, reflecting compromised vascular function. These findings suggest that SPS-sensitize neuroendocrine, autonomic, and vascular pathways create a state of cardiovascular vulnerability that could predispose individuals to hypertension when exposed to additional stressors. Understanding these mechanisms provides critical insights into the pathophysiology of stress-related cardiovascular disorders and underscores the need for targeted therapeutic interventions that address oxidative stress and modulate altered PVN pathways to mitigate the cardiovascular impact of PTSD and related conditions. Full article

(This article belongs to the Special Issue Harnessing Antioxidants: Pioneering Approaches in Cardiovascular Disease Prevention and Therapy)

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17 pages, 4561 KiB

Open AccessArticle

Ole-Oxy, a Semi-Synthetic Analog of Oleuropein, Ameliorates Acute Skin and Colon Inflammation in Mice

by Nikolaos V. Angelis, Efthymios Paronis, Georgia Sarikaki, Antonios Kyriakopoulos, Anna Agapaki, Pigi-Maria Niotopoulou, Christina C. Knai, Pavlos Alexakos, Odyssefs Liagkas, Konstantinos F. Mavreas, Constantin N. Baxevanis, Alexios-Leandros Skaltsounis, Ourania E. Tsitsilonis and Ioannis K. Kostakis

Antioxidants 2024, 13(11), 1422; https://doi.org/10.3390/antiox13111422 - 20 Nov 2024

Viewed by 290

Abstract

Inflammation is a key process in the pathophysiology of various diseases, with macrophages playing a central role in the inflammatory response. This study investigates the anti-inflammatory potential of a newly synthesized analog of oleuropein (OP), the major olive tree (Olea europaea) metabolite. [...] Read more.

Inflammation is a key process in the pathophysiology of various diseases, with macrophages playing a central role in the inflammatory response. This study investigates the anti-inflammatory potential of a newly synthesized analog of oleuropein (OP), the major olive tree (Olea europaea) metabolite. This derivative of OP, named Ole-Oxy, was designed by introducing an oxygen atom between the aromatic ring and the aliphatic chain of OP, to enhance interaction with proteins and improve bioactivity. Ole-Oxy demonstrated notable anti-inflammatory effects in vitro, particularly in phorbol 12-myristate 13-acetate-differentiated THP-1 macrophages, where it markedly reduced interleukin-6, tumor necrosis factor-α, and reactive oxygen species (ROS) levels, surpassing the effects of OP. In vivo, Ole-Oxy was evaluated in mouse models of acute skin and colon inflammation, showing significant efficacy in C57BL/6J mice, likely due to their Th1-biased immune response. Our results suggest that Ole-Oxy modulates inflammation through ROS scavenging and differential macrophage activation, underscoring the need for further research to fully elucidate its mechanism of action and optimize its pharmacokinetic properties for future therapeutic applications. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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13 pages, 4441 KiB

Open AccessArticle

Mitochondrial Redox Status Regulates Glycogen Metabolism via Glycogen Phosphorylase Activity

by Ikko Sakamoto, Shuichi Shibuya, Hidetoshi Nojiri, Kotaro Takeno, Hiroshi Nishimune, Keisuke Yaku, Takashi Nakagawa, Muneaki Ishijima and Takahiko Shimizu

Antioxidants 2024, 13(11), 1421; https://doi.org/10.3390/antiox13111421 - 20 Nov 2024

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Abstract

Mitochondria and glycogen are co-distributed in skeletal muscles to regulate the metabolic status. Mitochondria are also redox centers that regulate the muscle function during exercise. However, the pathophysiological relationship between the mitochondrial redox status and glycogen metabolism in the muscle remains unclear. In [...] Read more.

Mitochondria and glycogen are co-distributed in skeletal muscles to regulate the metabolic status. Mitochondria are also redox centers that regulate the muscle function during exercise. However, the pathophysiological relationship between the mitochondrial redox status and glycogen metabolism in the muscle remains unclear. In the present study, we examined the pathological effects of mitochondrial dysfunction induced by mitochondrial superoxide dismutase (SOD2) depletion on glycogen metabolism. We found that muscle glycogen was significantly accumulated in association with motor dysfunction in mice with a muscle-specific SOD2 deficiency. Muscle glycogen phosphorylase (GP-M) activity, which is a key enzyme for glycogen degradation at times when energy is needed (e.g., during exercise), was significantly decreased in the mutant muscle. Moreover, the GP-M activity on normal muscle sections decreased after treatment with paraquat, a superoxide generator. In contrast, treatment with antioxidants reversed the GP-M activity and motor disturbance of the mutant mice, indicating that GP-M activity was reversibly regulated by the redox balance. These results demonstrate that the maintenance of the mitochondrial redox balance regulates glycogen metabolism via GP-M activity. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Function in Exercise and Physical Activity)

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17 pages, 10811 KiB

Open AccessArticle

Data-Driven Insights into the Association Between Oxidative Stress and Calcium-Regulating Proteins in Cardiovascular Disease

by Namuna Panday, Dibakar Sigdel, Irsyad Adam, Joseph Ramirez, Aarushi Verma, Anirudh N. Eranki, Wei Wang, Ding Wang and Peipei Ping

Antioxidants 2024, 13(11), 1420; https://doi.org/10.3390/antiox13111420 - 20 Nov 2024

Viewed by 459

Abstract

A growing body of biomedical literature suggests a bidirectional regulatory relationship between cardiac calcium (Ca²⁺)-regulating proteins and reactive oxygen species (ROS) that is integral to the pathogenesis of various cardiac disorders via oxidative stress (OS) signaling. To address the challenge of [...] Read more.

A growing body of biomedical literature suggests a bidirectional regulatory relationship between cardiac calcium (Ca²⁺)-regulating proteins and reactive oxygen species (ROS) that is integral to the pathogenesis of various cardiac disorders via oxidative stress (OS) signaling. To address the challenge of finding hidden connections within the growing volume of biomedical research, we developed a data science pipeline for efficient data extraction, transformation, and loading. Employing the CaseOLAP (Context-Aware Semantic Analytic Processing) algorithm, our pipeline quantifies interactions between 128 human cardiomyocyte Ca²⁺-regulating proteins and eight cardiovascular disease (CVD) categories. Our machine-learning analysis of CaseOLAP scores reveals that the molecular interfaces of Ca²⁺-regulating proteins uniquely associate with cardiac arrhythmias and diseases of the cardiac conduction system, distinguishing them from other CVDs. Additionally, a knowledge graph analysis identified 59 of the 128 Ca²⁺-regulating proteins as involved in OS-related cardiac diseases, with cardiomyopathy emerging as the predominant category. By leveraging a link prediction algorithm, our research illuminates the interactions between Ca²⁺-regulating proteins, OS, and CVDs. The insights gained from our study provide a deeper understanding of the molecular interplay between cardiac ROS and Ca²⁺-regulating proteins in the context of CVDs. Such an understanding is essential for the innovation and development of targeted therapeutic strategies. Full article

(This article belongs to the Special Issue Redox Regulation in Cardiovascular Diseases)

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Graphical abstract

19 pages, 2034 KiB

Open AccessArticle

Protective Contribution of Rosmarinic Acid in Rosemary Extract Against Copper-Induced Oxidative Stress

by Arian Kola, Ginevra Vigni, Stefania Lamponi and Daniela Valensin

Antioxidants 2024, 13(11), 1419; https://doi.org/10.3390/antiox13111419 - 19 Nov 2024

Viewed by 398

Abstract

Rosemary extract (Rosmarinus officinalis) is a natural source of bioactive compounds with significant antioxidant properties. Among these, rosmarinic acid is celebrated for its potent antioxidant, anti-inflammatory, antimicrobial, and neuroprotective properties, making it a valuable component in both traditional medicine and modern [...] Read more.

Rosemary extract (Rosmarinus officinalis) is a natural source of bioactive compounds with significant antioxidant properties. Among these, rosmarinic acid is celebrated for its potent antioxidant, anti-inflammatory, antimicrobial, and neuroprotective properties, making it a valuable component in both traditional medicine and modern therapeutic research. Neurodegenerative diseases like Alzheimer’s and Parkinson’s are closely linked to oxidative damage, and research indicates that rosmarinic acid may help protect neurons by mitigating this harmful process. Rosmarinic acid is able to bind cupric ions (Cu²⁺) and interfere with the production of reactive oxygen species (ROS) produced by copper through Fenton-like reactions. This study aims to further evaluate the contribution of rosmarinic acid within rosemary extract by comparing its activity to that of isolated rosmarinic acid. By using a detailed approach that includes chemical characterization, antioxidant capacity assessment, and neuroprotective activity testing, we have determined whether the combined components in rosemary extract enhance or differ from the effects of rosmarinic acid alone. This comparison is crucial for understanding whether the full extract offers added benefits beyond those of isolated rosmarinic acid in combating oxidative stress and Aβ-induced toxicity. Full article

(This article belongs to the Special Issue Redox Metals and Catecholamines in Neurodegenerative Diseases)

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14 pages, 2992 KiB

Open AccessArticle

Green Recovery and Identification of Antioxidant and Enzyme Inhibitor Molecules from Pisco Grape Pomace by Targeted Effects Analysis Using Thin-Layer Chromatography, Bioassay, and Mass Spectrometry

by Jacqueline Poblete, Joaquín Fernández-Martínez, Mario Aranda and Issis Quispe-Fuentes

Antioxidants 2024, 13(11), 1418; https://doi.org/10.3390/antiox13111418 - 19 Nov 2024

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Abstract

The search and identification of inhibitory molecules from novel natural sources, such as pisco grape pomace extract obtained by green techniques, may help to develop agents with therapeutic potential that are beneficial to health with fewer adverse effects than drugs. Many drugs act [...] Read more.

The search and identification of inhibitory molecules from novel natural sources, such as pisco grape pomace extract obtained by green techniques, may help to develop agents with therapeutic potential that are beneficial to health with fewer adverse effects than drugs. Many drugs act as enzyme inhibitors, decreasing their activity and thus correcting a metabolic imbalance. This study aims to identify bioactive molecules with antioxidant and inhibitory activity over acetylcholinesterase and cyclooxygenase enzymes present in pisco grape pomace green extracts. Bioactive molecules were detected and identified applying directed effect analysis on planar chromatography coupled to mass spectrometry. For the first time, the presence of antioxidant molecules (quercetin-3-O-glucuronide, quercetin-3-O-glucoside, and gallic acid) and inhibitors of acetylcholinesterase (kaempferol-3-O-glucoside) and cyclooxygenase (gallic acid) enzymes are reported in pisco grape pomace. According to the results, grape pomace could be an alternative to develop novel functional foods and nutraceuticals that provide health benefits and, at the same time, generate a circular economy in the industry. Full article

(This article belongs to the Special Issue Methodologies for Improving Antioxidant Properties and Absorption)

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35 pages, 4703 KiB

Open AccessReview

Edible Coatings for Fish Preservation: Literature Data on Storage Temperature, Product Requirements, Antioxidant Activity, and Coating Performance—A Review

by Mia Kurek, Petra Pišonić, Mario Ščetar, Tibor Janči, Iva Čanak, Sanja Vidaček Filipec, Nasreddine Benbettaieb, Frédéric Debeaufort and Kata Galić

Antioxidants 2024, 13(11), 1417; https://doi.org/10.3390/antiox13111417 - 19 Nov 2024

Viewed by 423

Abstract

Fresh fish is among the most nutritive foodstuffs, but it is also the most perishable one. Therefore, huge efforts have been made to find the most suitable tools to deliver fish of the highest quality to exigent consumers. Scientific studies help the industry [...] Read more.

Fresh fish is among the most nutritive foodstuffs, but it is also the most perishable one. Therefore, huge efforts have been made to find the most suitable tools to deliver fish of the highest quality to exigent consumers. Scientific studies help the industry to exploit the newest findings to scale up emerging industrial technologies. In this review article, the focus is on the latest scientific findings on edible films used for fish coatings and storage. Since today’s packaging processing and economy are governed by sustainability, naturality underpins packaging science. The synthesis of edible coatings, their components, processing advantages, and disadvantages are outlined with respect to the preservation requirements for sensitive fish. The requirements of coating properties are underlined for specific scenarios distinguishing cold and freezing conditions. This review raises the importance of antioxidants and their role in fish storage and preservation. A summary of their impact on physical, chemical, microbiological, and sensory alterations upon application in real fish is given. Studies on their influence on product stability, including pro-oxidant activity and the prevention of the autolysis of fish muscle, are given. Examples of lipid oxidation and its inhibition by the antioxidants embedded in edible coatings are given together with the relationship to the development of off-odors and other unwanted impacts. This review selects the most significant and valuable work performed in the past decade in the field of edible coatings whose development is on the global rise and adheres to food waste and sustainable development goals 2 (zero hunger), 3 (good health and well-being), and 12 (responsible consumption and production). Full article

(This article belongs to the Special Issue Antimicrobial and Antioxidants Capacities: Application in Food Packaging)

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19 pages, 2450 KiB

Open AccessArticle

Antioxidant and Anti-Inflammatory Effects of Opuntia Extracts on a Model of Diet-Induced Steatosis

by Irene Besné-Eseverri, María Ángeles Martín, Gloria Lobo, M. Pilar Cano, María P. Portillo and Jenifer Trepiana

Antioxidants 2024, 13(11), 1416; https://doi.org/10.3390/antiox13111416 - 19 Nov 2024

Viewed by 341

Abstract

Oxidative stress and inflammation are widely recognised as factors that can initiate and facilitate the development of MAFLD. The aim of this study is to analyse the effect of low and high doses of Opuntia stricta var. dillenii peel extract (L-OD and H-OD, [...] Read more.

Oxidative stress and inflammation are widely recognised as factors that can initiate and facilitate the development of MAFLD. The aim of this study is to analyse the effect of low and high doses of Opuntia stricta var. dillenii peel extract (L-OD and H-OD, respectively) and Opuntia ficus-indica var. colorada pulp extract (L-OFI and H-OFI, respectively), which are rich in betalains and phenolic compounds, on oxidative stress, inflammation, DNA damage and apoptosis in rat livers with diet-induced steatosis. Steatotic diet led to increased final body and liver weight, serum transaminases, hepatic TG content, oxidative status and cell death. H-OFI treatment decreased serum AST levels, while L-OFI reduced hepatic TG accumulation. Oxidative stress was partially prevented with H-OD and H-OFI supplementation, and pro-inflammatory cytokines levels were especially improved with H-OFI treatment. Moreover, H-OFI appears to prevent DNA damage markers. Finally, H-OD and L-OFI supplementation down-regulated the apoptotic pathway. In conclusion, both H-OD and H-OFI supplementation were effective in regulating the progression to metabolic steatohepatitis, triggering different mechanisms of action. Full article

(This article belongs to the Special Issue Antioxidants Therapy and Oxidative Stress in Non-alcoholic Fatty Liver Disease)

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19 pages, 4473 KiB

Open AccessArticle

Imeglimin Halts Liver Damage by Improving Mitochondrial Dysfunction in a Nondiabetic Male Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis

by Kosuke Kaji, Soichi Takeda, Satoshi Iwai, Norihisa Nishimura, Shinya Sato, Tadashi Namisaki, Takemi Akahane and Hitoshi Yoshiji

Antioxidants 2024, 13(11), 1415; https://doi.org/10.3390/antiox13111415 - 18 Nov 2024

Viewed by 430

Abstract

Imeglimin promotes glucose-stimulated insulin secretion in the pancreas in a glucose-dependent manner and inhibits gluconeogenesis in the liver. Meanwhile, imeglimin can improve mitochondrial function in hepatocytes. We used a nondiabetic metabolic dysfunction-associated steatohepatitis (MASH) model to examine the effects of imeglimin on MASH [...] Read more.

Imeglimin promotes glucose-stimulated insulin secretion in the pancreas in a glucose-dependent manner and inhibits gluconeogenesis in the liver. Meanwhile, imeglimin can improve mitochondrial function in hepatocytes. We used a nondiabetic metabolic dysfunction-associated steatohepatitis (MASH) model to examine the effects of imeglimin on MASH independent of its glucose-lowering action. Mice fed a choline-deficient high-fat diet (CDA-HFD) were orally administered imeglimin (100 and 200 mg/kg twice daily), and MASH pathophysiology was evaluated after 8 weeks. Moreover, an in vitro study investigated the effects of imeglimin on palmitic acid (PA)-stimulated lipid accumulation, apoptosis, and mitochondrial dysfunction in human hepatocytes. CDA-HFD-fed mice showed hepatic steatosis, inflammation, and fibrosis without hyperglycemia. Imeglimin reduced hepatic steatosis in response to increased expression of β-oxidation-related markers. Imeglimin reduced reactive oxygen species accumulation and increased mitochondrial biogenesis in CDA-HFD-fed mice. Consequently, imeglimin suppressed hepatocyte apoptosis and decreased macrophage infiltration with reduced proinflammatory cytokine expression, suppressing hepatic fibrosis development. PA-stimulated hepatocytes induced lipogenesis, inflammatory cytokine production, and apoptosis, which were significantly suppressed by imeglimin. In mitochondrial function, imeglimin improved PA-stimulated decrease in mitochondrial membrane potential, mitochondrial complexes activity, oxygen consumption rate, and mitochondrial biogenesis marker expression. In conclusion, imeglimin could contribute to prevention of MASH progression through suppressing de novo lipogenesis and enhancing fatty acid oxidation. Full article

(This article belongs to the Special Issue Antioxidants Therapy and Oxidative Stress in Non-alcoholic Fatty Liver Disease)

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15 pages, 6039 KiB

Open AccessArticle

Exogenous GABA-Ca Alleviates Growth Inhibition Induced by a Low-P Environment in Peanuts (Arachis hypogaea)

by Zhiyu Sun, Mingzhu Ma, Huan Liu, Dongbing Tao, Shaikh Amjad Salam, Xiaori Han, Yifei Liu and Jean Wan Hong Yong

Antioxidants 2024, 13(11), 1414; https://doi.org/10.3390/antiox13111414 - 18 Nov 2024

Viewed by 376

Abstract

Phosphorus (P) deficiency is a major global factor constraining peanut production. Exogenous γ-aminobutyric acid (GABA) and Ca²⁺ are essential to improve stress resilience in peanuts growing under low-P conditions. This study therefore examined the detailed physiological effects of GABA-Ca on restoring peanut [...] Read more.

Phosphorus (P) deficiency is a major global factor constraining peanut production. Exogenous γ-aminobutyric acid (GABA) and Ca²⁺ are essential to improve stress resilience in peanuts growing under low-P conditions. This study therefore examined the detailed physiological effects of GABA-Ca on restoring peanut growth under low-P conditions. These included the root–shoot ratio, leaf nutrients, photochemical activity, reactive oxygen species (ROS), cyclic electron flow (CEF), ATP synthase activity, and the proton gradient (∆pH), all of which were measured under low-P (LP, 0.5 mM) and optimized-P (1 mM) conditions. Specifically, supplying GABA-Ca under LP conditions regulated the ∆pH by causing adjustments in CEF and ATP synthase activities, buffering the photosystems’ activities, restoring the antioxidant enzyme system, and lowering ROS production. Interestingly, exogenous GABA-Ca restored peanut growth under low-P conditions, possibly by the putative signaling crosstalk between GABA and Ca²⁺. The plausible signal amplification between GABA and Ca²⁺ suggested that the combination of GABA and Ca, may offer an effective strategy for enhancing peanut adaptation to low-P conditions. Moving forward, the strategic supplementation of GABA-Ca, either during cultivation or through the formulation of novel fertilizers, opens up many possibilities for better and more resilient plant production in soils with low P. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants)

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13 pages, 478 KiB

Open AccessArticle

N-3 Fatty Acids in Seafood Influence the Association Between the Composite Dietary Antioxidant Index and Depression: A Community-Based Prospective Cohort Study

by Junhwi Moon, Minji Kim and Yangha Kim

Antioxidants 2024, 13(11), 1413; https://doi.org/10.3390/antiox13111413 - 18 Nov 2024

Viewed by 494

Abstract

Accumulating evidence suggests that seafood and its components, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with mental health. However, little is known regarding whether the status of n-3 polyunsaturated fatty acids (PUFAs) modify the effect of dietary antioxidants [...] Read more.

Accumulating evidence suggests that seafood and its components, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with mental health. However, little is known regarding whether the status of n-3 polyunsaturated fatty acids (PUFAs) modify the effect of dietary antioxidants on depression. The main purpose of study is to investigate longitudinal associations between seafood consumption and depression among 2564 participants aged 40–69 years using data from the Korean Genome and Epidemiology Study. The composite dietary antioxidant index (CDAI) and dietary intake were measured by a validated 106-item food frequency questionnaire and depression was assessed using the Beck Depression Inventory (BDI). The Cox’s proportional hazard model was used to examine the risk of depression according to seafood consumption. During an 8-year follow-up period, 165 (11.9%) men and 224 (18.9%) women experienced depression. After adjustment for confounders, the risk of depression was inversely associated with seafood consumption, with a 42% lower risk (HR _{T5 vs. T1} = 0.58, 95% CI: 0.35–0.98, p = 0.040) only being found among women. In a group with a high n-3 PUFA intake, CDAI scores were negatively correlated with BDI scores (r = −0.146, p < 0.001) among women. Seafood consumption might lead to more favorable outcomes against depression if accompanied by an increased intake of foods that are rich in antioxidants. Full article

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18 pages, 2965 KiB

Open AccessArticle

Determination of the Botanical Origin and Physicochemical Properties of a Propolis Sample Through an Integrated Methodology

by Jose Juan Alcivar-Saldaña, Marco Aurelio Rodriguez-Monroy, Arturo Aguirre-Gómez, Liborio Carrillo-Miranda, Benjamin Velasco-Bejarano and Maria Margarita Canales-Martinez

Antioxidants 2024, 13(11), 1412; https://doi.org/10.3390/antiox13111412 - 18 Nov 2024

Viewed by 318

Abstract

The growing interest in products of natural origin has led to the implementation of products such as propolis because they possess biological properties that are useful in the treatment of various ailments, so it is relevant to know the botanical origin of the [...] Read more.

The growing interest in products of natural origin has led to the implementation of products such as propolis because they possess biological properties that are useful in the treatment of various ailments, so it is relevant to know the botanical origin of the physicochemical compounds that provide propolis with its biological properties. To identify the floral sources that provide resources to bees for the manufacture of propolis, several methodologies have been implemented, such as palynological analysis, which, through pollen content, has made it possible to identify the plant species that provide resources to bees. On the other hand, analysis of the physicochemical components of propolis has revealed that phenols and flavonoids are mainly responsible for the biological activity of propolis. Evaluation of the antibacterial and antifungal potential of propolis revealed the inhibitory potential of both Gram (+) and Gram (−) bacteria, as well as Candida albicans. However, all these investigations have been carried out individually and not always with the same sample. Therefore, the objective of this research was to design a methodology that allows the use of a single sample of propolis and uses sufficient resources for different research areas to evaluate most of the physical and chemical properties of propolis, as well as its botanical origin. With the implemented methodology, it was possible to obtain sufficient resources that provided results for each of the research areas, taking advantage of the propolis sample. Full article

(This article belongs to the Special Issue Antioxidant and Antimicrobial Activity of Honey Bee Products—2nd Edition)

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24 pages, 3148 KiB

Open AccessArticle

Nitroxyl Hybrids with Curcumin and Stilbene Scaffolds Display Potent Antioxidant Activity, Remodel the Amyloid Beta Oligomer, and Reverse Amyloid Beta-Induced Cytotoxicity

by Madhu S. Budamagunta, Hidetoshi Mori, Joshua Silk, Ryan R. Slez, Balázs Bognár, Ulises Ruiz Mendiola, Tamás Kálai, Izumi Maezawa and John C. Voss

Antioxidants 2024, 13(11), 1411; https://doi.org/10.3390/antiox13111411 - 18 Nov 2024

Viewed by 331

Abstract

The disorder and heterogeneity of low-molecular-weight amyloid-beta oligomers (AβOs) underlie their participation in multiple modes of cellular dysfunction associated with the etiology of Alzheimer’s disease (AD). The lack of specified conformational states in these species complicates efforts to select or design small molecules [...] Read more.

The disorder and heterogeneity of low-molecular-weight amyloid-beta oligomers (AβOs) underlie their participation in multiple modes of cellular dysfunction associated with the etiology of Alzheimer’s disease (AD). The lack of specified conformational states in these species complicates efforts to select or design small molecules to targeting discrete pathogenic states. Furthermore, targeting AβOs alone may be therapeutically insufficient, as AD progresses as a multifactorial, self-amplifying cascade. To address these challenges, we have screened the activity of seven new candidates that serve as Paramagnetic Amyloid Ligand (PAL) candidates. PALs are bifunctional small molecules that both remodel the AβO structure and localize a potent antioxidant that mimics the activity of SOD within live cells. The candidates are built from either a stilbene or curcumin scaffold with nitroxyl moiety to serve as catalytic antioxidants. Measurements of PAL AβO binding and remolding along with assessments of bioactivity allow for the extraction of useful SAR information from screening data. One candidate (HO-4450; PMT-307), with a six-membered nitroxyl ring attached to a stilbene ring, displays the highest potency in protecting against cell-derived Aβ. A preliminary low-dose evaluation in AD model mice provides evidence of modest treatment effects by HO-4450. The results for the curcumin PALs demonstrate that the retention of the native curcumin phenolic groups is advantageous to the design of the hybrid PAL candidates. Finally, the PAL remodeling of AβO secondary structures shows a reasonable correlation between a candidate’s bioactivity and its ability to reduce the fraction of antiparallel β-strand. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)

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3 pages, 1801 KiB

Open AccessCorrection

Correction: Mahmoud et al. Coriander Oil Reverses Dexamethasone-Induced Insulin Resistance in Rats. Antioxidants 2022, 11, 441

by Mona F. Mahmoud, Noura Ali, Islam Mostafa, Rehab A. Hasan and Mansour Sobeh

Antioxidants 2024, 13(11), 1410; https://doi.org/10.3390/antiox13111410 - 18 Nov 2024

Viewed by 176

Abstract

In the original publication [...] Full article

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16 pages, 2842 KiB

Open AccessArticle

Polyphenolic Antioxidants in Bilberry Stems and Leaves: A Non-Targeted Analysis by Two-Dimensional NMR Spectroscopy and Liquid Chromatography–High-Resolution Mass Spectrometry

by Anna V. Faleva, Nikolay V. Ulyanovskii, Alexandra A. Onuchina and Dmitry S. Kosyakov

Antioxidants 2024, 13(11), 1409; https://doi.org/10.3390/antiox13111409 - 17 Nov 2024

Viewed by 668

Abstract

Compared with those of berries, the stems and leaves of the genus Vaccinium are important and underestimated sources of polyphenols with high antioxidant activity. In the course of this work, aqueous methanol extracts of the aerial parts of common bilberry (Vaccinium myrtillus [...] Read more.

Compared with those of berries, the stems and leaves of the genus Vaccinium are important and underestimated sources of polyphenols with high antioxidant activity. In the course of this work, aqueous methanol extracts of the aerial parts of common bilberry (Vaccinium myrtillus L.) and bog bilberry (Vaccinium uliginosum L.) were studied to analyze the component compositions of their biologically active polyphenolic compounds. The aqueous methanol fractions of the stems and leaves of the studied samples contained 8.7 and 4.6% extractives, respectively, and were comparable in total polyphenol content, but presented significant differences in antioxidant activity. The identification of polyphenolic compounds was carried out via the following two-stage analytical procedure: (1) non-targeted screening of dominant structures via the 2D NMR method and (2) analysis of HPLC-HRMS data via the scanning of precursor ions for a specific ion. A total of 56 phenolic compounds were identified, including the glycosides quercetin, proanthocyanidins, and catechins, as well as various conjugates of caffeic and p-coumaric acids, including iridoids. Some of the latter, such as caffeoyl and p-coumaroyl hydroxydihydromonotropein, as well as a number of lignan glycosides, were described for the first time in V. uliginósum and V. myrtillus. Full article

(This article belongs to the Special Issue Modern Analytical Approaches in the Identification of Polyphenols in Food, Food Sub-Products and Plant Matrices)

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21 pages, 2094 KiB

Open AccessArticle

Influence of the Degree of Unsaturation in Fish Oil Supplements on Oxidative Stress and Protein Carbonylation in the Cerebral Cortex and Cerebellum of Healthy Rats

by Francisco Moreno, Lucía Méndez, Ingrid Fernández, Bernat Miralles-Pérez, Montserrat Giralt, Marta Romeu, Sara Ramos-Romero, Josep Lluís Torres and Isabel Medina

Antioxidants 2024, 13(11), 1408; https://doi.org/10.3390/antiox13111408 - 17 Nov 2024

Viewed by 613

Abstract

ω-3 polyunsaturated fatty acids (PUFAs) are crucial for brain structure and function, especially docosahexaenoic acid (DHA). However, an excess of DHA may increase lipid peroxidation due to its high degree of unsaturation, particularly in tissues highly susceptible to oxidative stress, such as the [...] Read more.

ω-3 polyunsaturated fatty acids (PUFAs) are crucial for brain structure and function, especially docosahexaenoic acid (DHA). However, an excess of DHA may increase lipid peroxidation due to its high degree of unsaturation, particularly in tissues highly susceptible to oxidative stress, such as the brain. Therefore, this study evaluated the effects of 10 weeks of dietary supplementation with fish oil containing 80% DHA on oxidative stress and the modulation of the carbonylated proteome in both the cerebral cortex and cerebellum of male Sprague Dawley rats. The results were compared with those induced by oils with a lower degree of fat unsaturation (fish oil containing 25% DHA and 25% eicosapentaenoic acid, soybean oil containing 50% linoleic acid and coconut oil containing 90% saturated fat). The results demonstrated that fish oil containing 80% DHA significantly increased the ω3/ω6 ratio in both the cortex and cerebellum while stimulating antioxidant defense by enhancing the reduced glutathione amount and decreasing the carbonylation of specific proteins, mainly those involved in glycolysis and neurotransmission. The majority of sensitive proteins in both brain regions followed this carbonylation trend (in decreasing order): soybean > EPA/DHA 1:1 > coconut > 80% DHA. The results also indicated that the cerebellum is more responsive than the cortex to changes in the cellular redox environment induced by varying degrees of fat unsaturation. In conclusion, under healthy conditions, dietary supplementation with fish oils containing high DHA levels makes the brain more resilient to potential oxidative insults compared to oils with lower DHA content and a lower degree of fatty acid unsaturation. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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20 pages, 8203 KiB

Open AccessArticle

An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells

by Minjin Jeong, Sho Kurihara and Konstantina M. Stankovic

Antioxidants 2024, 13(11), 1407; https://doi.org/10.3390/antiox13111407 - 16 Nov 2024

Viewed by 426

Abstract

The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise [...] Read more.

The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise mechanisms remain unclear due to the limitations of animal models and challenges of obtaining living human inner ear tissue. Therefore, we developed an in vitro oxidative stress model of the pre-natal human inner ear using otic progenitor cells (OPCs) derived from human-induced pluripotent stem cells (hiPSCs). OPCs, hiPSCs, and HeLa cells were exposed to hydrogen peroxide or ototoxic drugs (gentamicin and cisplatin) that induce oxidative stress to evaluate subsequent cell viability, cell death, reactive oxygen species (ROS) production, mitochondrial activity, and apoptosis (caspase 3/7 activity). Dose-dependent reductions in OPC cell viability were observed post-exposure, demonstrating their vulnerability to oxidative stress. Notably, gentamicin exposure induced ROS production and cell death in OPCs, but not hiPSCs or HeLa cells. This OPC-based human model effectively simulates oxidative stress conditions in the human inner ear and may be useful for modeling the impact of ototoxicity during early pregnancy or evaluating therapies to prevent cytotoxicity. Full article

(This article belongs to the Special Issue Oxidative Stress in Hearing Loss)

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32 pages, 2311 KiB

Open AccessArticle

Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function

by Manuela Moriggi, Lucia Ruggiero, Enrica Torretta, Dario Zoppi, Beatrice Arosio, Evelyn Ferri, Alessandra Castegna, Chiara Fiorillo, Cecilia Gelfi and Daniele Capitanio

Antioxidants 2024, 13(11), 1406; https://doi.org/10.3390/antiox13111406 - 16 Nov 2024

Viewed by 371

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely [...] Read more.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely impair muscle function, ultimately resulting in a loss of ambulation. A thorough analysis of molecular factors associated with the varying degrees of muscle impairment in FSHD is still lacking. This study investigates the molecular mechanisms and biomarkers in the biceps brachii of FSHD patients, classified according to the FSHD clinical score, the A-B-C-D classification scheme, and global proteomic variation. Our findings reveal distinct metabolic signatures and compensatory responses in patients. In severe cases, we observe pronounced metabolic dysfunction, marked by dysregulated glycolysis, activation of the reductive pentose phosphate pathway (PPP), a shift toward a reductive TCA cycle, suppression of oxidative phosphorylation, and an overproduction of antioxidants that is not matched by an increase in the redox cofactors needed for their function. This imbalance culminates in reductive stress, exacerbating muscle wasting and inflammation. In contrast, mild cases show metabolic adaptations that mitigate stress by activating polyols and the oxidative PPP, preserving partial energy flow through the oxidative TCA cycle, which supports mitochondrial function and energy balance. Furthermore, activation of the hexosamine biosynthetic pathway promotes autophagy, protecting muscle cells from apoptosis. In conclusion, our proteomic data indicate that specific metabolic alterations characterize both mild and severe FSHD patients. Molecules identified in mild cases may represent potential diagnostic and therapeutic targets for FSHD. Full article

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15 pages, 1382 KiB

Open AccessReview

Glutathione Peroxidases: An Emerging and Promising Therapeutic Target for Pancreatic Cancer Treatment

by Paula Iglesias-Matesanz, Carlos Lacalle-Gonzalez, Carlos Lopez-Blazquez, Michael Ochieng’ Otieno, Jesus Garcia-Foncillas and Javier Martinez-Useros

Antioxidants 2024, 13(11), 1405; https://doi.org/10.3390/antiox13111405 - 16 Nov 2024

Viewed by 488

Abstract

Glutathione peroxidases (GPxs) are a family of enzymes that play a critical role in cellular redox homeostasis through the reduction of lipid hydroperoxides to alcohols, using glutathione as a substrate. Among them, GPx4 is particularly of interest in the regulation of ferroptosis, a [...] Read more.

Glutathione peroxidases (GPxs) are a family of enzymes that play a critical role in cellular redox homeostasis through the reduction of lipid hydroperoxides to alcohols, using glutathione as a substrate. Among them, GPx4 is particularly of interest in the regulation of ferroptosis, a form of iron-dependent programmed cell death driven by the accumulation of lipid peroxides in the endoplasmic reticulum, mitochondria, and plasma membrane. Ferroptosis has emerged as a crucial pathway in the context of cancer, particularly pancreatic cancer, which is notoriously resistant to conventional therapies. GPx4 acts as a key inhibitor of ferroptosis by detoxifying lipid peroxides, thereby preventing cell death. However, this protective mechanism also enables cancer cells to survive under oxidative stress, which makes GPx4 a potential druggable target in cancer therapy. The inhibition of GPx4 can trigger ferroptosis selectively in cancer cells, especially in those that rely heavily on this pathway for survival, such as pancreatic cancer cells. Consequently, targeting GPx4 and other GPX family members offers a promising therapeutic strategy to sensitize pancreatic cancer cells to ferroptosis, potentially overcoming resistance to current treatments and improving patient outcomes. Current research is focusing on the development of small-molecule inhibitors of GPx4 as potential candidates for pancreatic cancer treatment. Full article

(This article belongs to the Special Issue Redox-Modulating Strategies in Cancer Therapy: Targeted Thioredoxin System Inhibition)

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5 pages, 219 KiB

Open AccessEditorial

Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III

by Chiara Nediani, Jessica Ruzzolini and Monica Dinu

Antioxidants 2024, 13(11), 1404; https://doi.org/10.3390/antiox13111404 - 16 Nov 2024

Viewed by 405

Abstract

Non-communicable diseases (NCDs), including cardiovascular diseases, diabetes, and neurodegenerative disorders, pose a significant global health challenge [...] Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

5 pages, 796 KiB

Open AccessEditorial

Oxidative Stress and Inflammation in Cancer

by Daniela Sorriento

Antioxidants 2024, 13(11), 1403; https://doi.org/10.3390/antiox13111403 - 15 Nov 2024

Viewed by 491

Abstract

Reactive oxygen species (ROS) are important signaling molecules, physiologically synthesized by oxygen metabolism [...] Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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18 pages, 3815 KiB

Open AccessArticle

Persulfidation of Human Cystathionine γ-Lyase Inhibits Its Activity: A Negative Feedback Regulation Mechanism for H₂S Production

by Guanya Jia, Heng Li, Haisheng Gan, Jun Wang, Zhilong Zhu, Yanxiong Wang, Yongyi Ye, Xiaoya Shang and Weining Niu

Antioxidants 2024, 13(11), 1402; https://doi.org/10.3390/antiox13111402 - 15 Nov 2024

Viewed by 389

Abstract

Cystathionine γ-lyase (CSE) is the second enzyme in the trans-sulfuration pathway that converts cystathionine to cysteine. It is also one of three major enzymes responsible for the biosynthesis of hydrogen sulfide (H₂S). CSE is believed to be the major source of [...] Read more.

Cystathionine γ-lyase (CSE) is the second enzyme in the trans-sulfuration pathway that converts cystathionine to cysteine. It is also one of three major enzymes responsible for the biosynthesis of hydrogen sulfide (H₂S). CSE is believed to be the major source of endogenous H₂S in the cardiovascular system, and the CSE/H₂S system plays a crucial role in a variety of physiological and pathological processes. However, the regulatory mechanism of the CSE/H₂S system is less well understood, especially at the post-translational level. Here, we demonstrated that the persulfidation of CSE inhibits its activity by ~2-fold in vitro. The loss of this post-translational modification in the presence of dithiothreitol (DTT) results in a reversal of basal activity. Cys137 was identified as the site for persulfidation by combining mass spectrometry, mutagenesis, activity analysis and streptavidin–biotin pull-down assays. To test the physiological relevance of the persulfidation regulation of CSE, human aortic vascular smooth muscle cells (HA-VSMCs) were incubated with vascular endothelial growth factor (VEGF), which is known to enhance endogenous H₂S levels. Under these conditions, consistent with the change tendency of the cellular H₂S level, the CSE persulfidation levels increased transiently and then gradually decreased to the basal level. Collectively, our study revealed a negative feedback regulation mechanism of the CSE/H₂S system via the persulfidation of CSE and demonstrated the potential for maintaining cellular H₂S homeostasis under oxidative stress conditions, particularly in tissues where CSE is a major source of H₂S. Full article

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15 pages, 2045 KiB

Open AccessArticle

Oxidative Stress in an African Ground Squirrel, a Case of Healthy Aging and Reproduction

by Paul Juan Jacobs, Sjoerd Vos, Chelsea E. Bishop, Daniel William Hart, Nigel Charles Bennett and Jane M. Waterman

Antioxidants 2024, 13(11), 1401; https://doi.org/10.3390/antiox13111401 - 15 Nov 2024

Viewed by 296

Abstract

Oxidative stress plays a crucial role in mediating life-history processes, where it can compromise survival and reproduction through harmful alterations to DNA, lipids, and proteins. In this study, we investigated oxidative stress in Cape ground squirrels (Xerus inauris), a longer-lived African [...] Read more.

Oxidative stress plays a crucial role in mediating life-history processes, where it can compromise survival and reproduction through harmful alterations to DNA, lipids, and proteins. In this study, we investigated oxidative stress in Cape ground squirrels (Xerus inauris), a longer-lived African ground squirrel species with a high reproductive skew and unique life history strategies. We measured oxidative stress as total antioxidant capacity (TAC), total oxidant status (TOS), and an oxidative stress index (OSI) in blood plasma from individuals of approximately known ages. Our results reveal a distinct pattern of decreasing oxidative stress with age, consistent across both sexes. Females exhibited lower OSI and TOS levels than males. Males employing different life-history strategies, namely natal (staying at home), had significantly lower oxidative stress compared to the band (roaming male groups), likely due to variations in metabolic rate, activity, and feeding rates. However, both strategies exhibited reduced oxidative stress with age, though the underlying mechanisms require further investigation. We propose that selection pressures favoring survival contributed to the observed reduction in oxidative stress with age, potentially maximizing lifetime reproductive success in this species. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction of Mammals)

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39 pages, 1382 KiB

Open AccessSystematic Review

The Use of Antioxidants for Cardiovascular Protection in Fetal Growth Restriction: A Systematic Review

by Charmaine R. Rock, Suzanne L. Miller and Beth J. Allison

Antioxidants 2024, 13(11), 1400; https://doi.org/10.3390/antiox13111400 - 15 Nov 2024

Viewed by 363

Abstract

Fetal growth restriction (FGR) increases the risk of cardiovascular disease. There are currently no treatment options available; however, antioxidants have shown potential to improve cardiovascular deficits associated with FGR. This systematic review aimed to determine whether antenatal antioxidant intervention can effectively protect the [...] Read more.

Fetal growth restriction (FGR) increases the risk of cardiovascular disease. There are currently no treatment options available; however, antioxidants have shown potential to improve cardiovascular deficits associated with FGR. This systematic review aimed to determine whether antenatal antioxidant intervention can effectively protect the developing cardiovascular system in FGR. We searched for interventional studies that used an antenatal antioxidant intervention to improve cardiac and/or vascular outcomes in FGR published between 01/1946 and 09/2024 using MEDLINE and Embase (PROSPERO: CRD42024503756). The risk of bias was assessed with SYRCLE. The studies were assessed for cardiovascular protection based on the percentage of cardiac and/or vascular deficits that were restored with the antioxidant treatment. Studies were characterised as showing strong cardiovascular protection (≥50% restoration), mild cardiovascular protection (>0% but <50% restoration), an antioxidant-only effect (this did not include control group which showed a change with antioxidant intervention compared to FGR) or no cardiovascular protection (0% restoration). Thirty-eight publications met the inclusion criteria, encompassing 43 studies and investigating 15 antioxidant interventions. Moreover, 29/43 studies (71%) reported the restoration of at least one cardiac or vascular deficit with antioxidant intervention, and 21/43 studies (51%) were classified as strong cardiovascular protection. An ex vivo analysis of the arterial function in seven studies revealed endothelial dysfunction in growth-restricted offspring and antioxidant interventions restored the endothelial function in all cases. Additionally, four studies demonstrated that antioxidants reduced peroxynitrite-mediated oxidative stress. Notably, only 13/43 studies (32%) delayed antioxidant administration until after the induction of FGR. Antenatal antioxidant interventions show promise for providing cardiovascular protection in FGR. Melatonin was the most frequently studied intervention followed by nMitoQ, vitamin C and N-acetylcysteine, all of which demonstrated a strong capacity to reduce oxidative stress and improve nitric oxide bioavailability in the cardiovascular system of growth-restricted offspring; however, this systematic review highlights critical knowledge gaps and inconsistencies in preclinical research, which hinder our ability to determine which antioxidant treatments are currently suitable for clinical translation. Full article

(This article belongs to the Special Issue Early Metabolic Programming Mediated by Oxidative Stress)

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