Antioxidants

30 pages, 1449 KiB

Open AccessReview

Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress

by Xenia Abadin, Cristina de Dios, Marlene Zubillaga, Elia Ivars, Margalida Puigròs, Montserrat Marí, Albert Morales, Marisa Vizuete, Javier Vitorica, Ramon Trullas, Anna Colell and Vicente Roca-Agujetas

Antioxidants 2024, 13(12), 1440; https://doi.org/10.3390/antiox13121440 - 22 Nov 2024

Abstract

A shared hallmark of age-related neurodegenerative diseases is the chronic activation of innate immune cells, which actively contributes to the neurodegenerative process. In Alzheimer’s disease, this inflammatory milieu exacerbates both amyloid and tau pathology. A similar abnormal inflammatory response has been reported in [...] Read more.

A shared hallmark of age-related neurodegenerative diseases is the chronic activation of innate immune cells, which actively contributes to the neurodegenerative process. In Alzheimer’s disease, this inflammatory milieu exacerbates both amyloid and tau pathology. A similar abnormal inflammatory response has been reported in Parkinson’s disease, with elevated levels of cytokines and other inflammatory intermediates derived from activated glial cells, which promote the progressive loss of nigral dopaminergic neurons. Understanding the causes that support this aberrant inflammatory response has become a topic of growing interest and research in neurodegeneration, with high translational potential. It has been postulated that the phenotypic shift of immune cells towards a proinflammatory state combined with the presence of immunogenic cell death fuels a vicious cycle in which mitochondrial dysfunction plays a central role. Mitochondria and mitochondria-generated reactive oxygen species are downstream effectors of different inflammatory signaling pathways, including inflammasomes. Dysfunctional mitochondria are also recognized as important producers of damage-associated molecular patterns, which can amplify the immune response. Here, we review the major findings highlighting the role of mitochondria as a checkpoint of neuroinflammation and immunogenic cell deaths in neurodegenerative diseases. The knowledge of these processes may help to find new druggable targets to modulate the inflammatory response. Full article

(This article belongs to the Special Issue Mitochondrial Oxidative Stress in Aging and Disease—2nd Edition)

23 pages, 4525 KiB

Open AccessReview

Potential Opportunities for Pharmacogenetic-Based Therapeutic Exploitation of Xanthine Dehydrogenase in Cardiovascular Disease

by Gianmichele Massimo, Nicki Dyson, Fisayo Olotu, Rayomand S. Khambata and Amrita Ahluwalia

Antioxidants 2024, 13(12), 1439; https://doi.org/10.3390/antiox13121439 - 22 Nov 2024

Abstract

The majority of naturally occurring mutations of the human gene XDH, are associated with reduced or completely absent xanthine oxidoreductase (XOR) activity, leading to a disease known as classical xanthinuria, which is due to the accumulation and excretion of xanthine in urine. [...] Read more.

The majority of naturally occurring mutations of the human gene XDH, are associated with reduced or completely absent xanthine oxidoreductase (XOR) activity, leading to a disease known as classical xanthinuria, which is due to the accumulation and excretion of xanthine in urine. Three types of classical xanthinuria have been identified: type I, characterised by XOR deficiency, type II, caused by XOR and aldehyde oxidase (AO) deficiency, and type III due to XOR, AO, and sulphite oxidase (SO) deficiency. Type I and II are considered rare autosomal recessive disorders, a condition where two copies of the mutated gene must be present to develop the disease or trait. In most cases, xanthinuria type I and II result to be asymptomatic, and only occasionally lead to renal failure due to urolithiasis caused by xanthine deposition. However, in the last 10–15 years, new observations have been made about the link between naturally occurring mutations and pathological phenotypes particularly pertinent to cardiovascular diseases (CVD). These links have been attributed to a genetically driven increase of XOR expression and activity that is responsible for what is thought to be damaging uric acid (UA) and reactive oxygen species (ROS) accumulation, nitric oxide (·NO) depletion and endothelial dysfunction. In this review, we discuss the importance of genetics for interindividual variability of XOR expression and activity while focusing mainly on those variants thought to be relevant for CVD. In addition, we discuss the potential exploitation of the genetically driven increase of XOR activity to deliver more beneficial bioavailable ·NO. Finally, we examine the effect that non-synonymous mutations have on the tertiary structure of the protein and consequently on its capacity to interact with glycosaminoglycans (GAGs) localised on the outer surface of endothelial cells. Full article

(This article belongs to the Special Issue NO and ROS in Redox Signalling)

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16 pages, 1476 KiB

Open AccessArticle

Enrichment of Breadsticks with Flavoured Oils: Chemical Composition, Antioxidant Activity and Technological and Sensory Properties

by Vincenzo Sicari, Antonio Mincione, Irene Maria Grazia Custureri, Roberta Pino and Monica Rosa Loizzo

Antioxidants 2024, 13(12), 1438; https://doi.org/10.3390/antiox13121438 - 22 Nov 2024

Abstract

The present work compares the physical–chemical, organoleptic and antioxidant characteristics of breadsticks (Bs) prepared in the traditional way (BCs) with extra virgin olive oil (EVOO), and with mace (BMs), ginger (BGs) and turmeric (BTs) flavoured olive oil (FOO). Breadsticks’ water activity (a_w [...] Read more.

The present work compares the physical–chemical, organoleptic and antioxidant characteristics of breadsticks (Bs) prepared in the traditional way (BCs) with extra virgin olive oil (EVOO), and with mace (BMs), ginger (BGs) and turmeric (BTs) flavoured olive oil (FOO). Breadsticks’ water activity (a_w), pH, moisture content (U.R.), total phenol (TPC) and total flavonoid (TFC) content, colorimetric analysis and texture and sensory analysis were used to evaluate the impact of the new recipes on consumer acceptance. The radical scavenging activity was also assessed by using 1,1-diphenyl-2-picryl hydrazine (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS). The use of FOO influenced breadsticks’ colour with reference to the BG and BT enriched breadsticks, and some variability in free acidity values emerged from the comparison between EVOO and FOO. As expected, peroxide values increased in all enriched breadsticks. Moreover, all flavoured breadsticks were more resistant to lipid oxidation than BCs with an IP value of 92.44, 91.26 and 60.07 h, respectively, for BMs, BGs and BTs. The cooking process of the breadsticks at 180 °C for 25 min did not significantly impact the content of bioactive compounds. BMs showed the highest TPC and TFC with values of 996.32 and 534.41 mg/kg, respectively. Moreover, BMs showed the highest DPPH radical scavenging potential with a value of 393.91 µM TEAC/100 g extract, whereas BGs showed the highest ABTS radical scavenging activity (160.13 µM TEAC/100 g extract). Sensory quantitative descriptive analysis showed the most interesting parameters to be the intensity of toasting for BGs and the intensity of spiciness in BMs. Furthermore, BGs and BTs were found to have a slightly more pungent odour. From the texture assessment, the BC was the crumbliest breadstick, while greater crunchiness was found in the BG and BM samples. Full article

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13 pages, 1855 KiB

Open AccessArticle

Treatment with Pterostilbene Ameliorates the Antioxidant Status of Bovine Spermatozoa and Modulates Cell Death Pathways

by Christos Chavas, Vasiliki G. Sapanidou, Konstantinos Feidantsis, Sophia N. Lavrentiadou, Despoina Mavrogianni, Ioanna Zarogoulidou, Dimitrios J. Fletouris and Maria P. Tsantarliotou

Antioxidants 2024, 13(12), 1437; https://doi.org/10.3390/antiox13121437 - 22 Nov 2024

Abstract

Reactive Oxygen Species (ROS) play an important role in sperm physiology. They are required in processes such as capacitation and fertilization. However, the exposure of spermatozoa to ROS generated from internal or external sources may create a potentially detrimental redox imbalance. Antioxidant supplementation [...] Read more.

Reactive Oxygen Species (ROS) play an important role in sperm physiology. They are required in processes such as capacitation and fertilization. However, the exposure of spermatozoa to ROS generated from internal or external sources may create a potentially detrimental redox imbalance. Antioxidant supplementation in semen is now a rather common approach to protect spermatozoa from oxidative stress (OS) during their handling and/or cryopreservation. Supplementation with pterostilbene, a potent antioxidant, protects spermatozoa from OS and ameliorates their post-thawing characteristics and viability. In the present study, we used freezing/thawing as a model of natural ROS overproduction and investigated the molecular mechanisms modulated by pterostilbene. Specifically, bovine frozen/thawed spermatozoa were incubated with 10 or 25 μM pterostilbene for 60 min. Results have shown that in a dose-independent manner, pterostilbene decreased lipid peroxidation and increased intracellular GSH levels. Moreover, pterostilbene ameliorated energy production, as ATP and AMP/ATP levels were restored, and increased autophagy levels through AMP-activated protein kinase (AMPK) activation, which finally resulted in the inhibition of apoptotic cell death in bovine spermatozoa when exposed to OS. This study sheds light on spermatozoa redox state, the crosstalk between apoptotic and autophagic pathways, and its role in determining the beneficial or detrimental effect of ROS in spermatozoa. Full article

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

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20 pages, 7440 KiB

Open AccessArticle

A Comprehensive Study of Reactive Oxygen Species Explicit Dosimetry for Pleural Photodynamic Therapy

by Hongjing Sun, Yihong Ong, Michele M. Kim, Andreea Dimofte, Sunil Singhal, Keith A. Cengel, Arjun G. Yodh and Timothy C. Zhu

Antioxidants 2024, 13(12), 1436; https://doi.org/10.3390/antiox13121436 - 22 Nov 2024

Abstract

Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (¹O₂) through Type II photochemical reactions, along with superoxide anion radicals (O₂^•−), hydrogen [...] Read more.

Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (¹O₂) through Type II photochemical reactions, along with superoxide anion radicals (O₂^•−), hydrogen peroxide (H₂O₂), and hydroxyl radicals (^•OH) through Type I mechanisms. Accurate dosimetry, accounting for all three components, is crucial for predicting and optimizing PDT outcomes. Conventional dosimetry tracks only light fluence rate and photosensitizer concentration, neglecting the role of tissue oxygenation. Reactive oxygen species explicit dosimetry (ROSED) quantifies the reacted oxygen species concentration ([ROS]_rx) by explicit measurements of light fluence (rate), photosensitizer concentration, and tissue oxygen concentration. Here we determine tissue oxygenation from non-invasive diffuse correlation spectroscopy (DCS) measurement of tumor blood flow using a conversion factor established preclinically. In this study, we have enrolled 24 pleural PDT patients into the study. Of these patients, we are able to obtain data on 20. Explicit dosimetry of light fluence, Photofrin concentration, and tissue oxygenation concentrations were integrated into the ROSED model to calculate [ROS]_rx across multiple sites inside the pleural cavity and among different patients. Large inter- and intra-patient heterogeneities in [ROS]_rx were observed, despite identical 60 J/cm² light doses, with mean [ROS]_rx,meas of 0.56 ± 0.26 mM for 13 patients with 21 sites, and [ROS]_rx,calc1 of 0.48 ± 0.23 mM for 20 patients with 76 sites. This study presented the first comprehensive analysis of clinical ROSED in pleural mesothelioma patients, providing valuable data on future ROSED based pleural PDT that can potentially produce uniform ROS and thus improve the PDT efficacy for Photofrin-mediated pleural PDT. Full article

(This article belongs to the Special Issue Reactive Oxygen Species and Growth Factors in Photodynamic Therapy (PDT), Photobiomodulation (PBM), and Radiation Therapy (RT))

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40 pages, 4098 KiB

Open AccessArticle

Differential Biological Effects of Trifolium pratense Extracts—In Vitro Studies on Breast Cancer Models

by Lucian Albulescu, Alexandru Suciu, Mihaela Neagu, Cristiana Tanase and Sevinci Pop

Antioxidants 2024, 13(12), 1435; https://doi.org/10.3390/antiox13121435 - 22 Nov 2024

Abstract

The increasing popularity of herbal supplements emphasizes the need of scientific data regarding their health benefits and possible toxicological concerns. The complexity of botanical extracts, which include thousands of distinct compounds, contributes to the challenging nature of this endeavor. In this study, we [...] Read more.

The increasing popularity of herbal supplements emphasizes the need of scientific data regarding their health benefits and possible toxicological concerns. The complexity of botanical extracts, which include thousands of distinct compounds, contributes to the challenging nature of this endeavor. In this study, we explored the hormetic effects of two Trifolium pratense extracts on breast cell lines. Using a wide range of concentrations (0.1 to 3.33 mg/mL), we analyzed how extracts modulate cellular processes such as viability, proliferation, and oxidative stress on breast adenocarcinoma highly invasive estrogen receptor negative (ER-) and noninvasive ER+ cells, as well as on non-tumorigenic ER- normal cells. The cytotoxicity and real-time cell analysis (RTCA) assays showed that both extracts exercised a biphasic dose effect on adenocarcinoma ER+ and normal ER- cell proliferation and oxidative stress. We report a monotonic dose-dependent cytotoxicity on highly invasive adenocarcinoma ER- cells; the induced apoptosis was based on the pro-oxidant activity of extracts. The reactive oxygen species (ROS) generation by high-dose ethanolic extract was observed in all cells, followed by mitochondria dysfunction. Oxidative stress parameters, such as malondialdehyde (MDA) and reduced glutathione (GSH) levels, and superoxide dismutase (SOD) activity were affected. Our study demonstrates that T. pratense extracts have chemoprevention potential in normal and tumorigenic breast cells by modulating cellular proliferation and oxidative stress. Full article

(This article belongs to the Special Issue Exploring Recent Advances in Plant Extracts: Understanding Antioxidant Mechanisms and Health Benefits)

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15 pages, 1028 KiB

Open AccessArticle

Healthier Lipid Profiles of Japanese Adults, Especially in Women with Elevated High-Density Lipoprotein Cholesterol (HDL-C), Are Associated with Low HDL-C Peroxide Content

by Loni Berkowitz-Fiebich, Shelby M. Flaherty, Shinobu Kitayama, Mayumi Karasawa, Norito Kawakami, Attilio Rigotti and Christopher L. Coe

Antioxidants 2024, 13(12), 1434; https://doi.org/10.3390/antiox13121434 - 22 Nov 2024

Abstract

Japanese adults typically have healthier lipid profiles than American and European adults, who have been associated with a lower prevalence of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship [...] Read more.

Japanese adults typically have healthier lipid profiles than American and European adults, who have been associated with a lower prevalence of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults. Blood samples were collected from 463 participants, 31–84 years of age, who lived in Tokyo. A second blood sample was collected 5 years later from 241 of the participants, allowing us to evaluate the temporal stability of the inverse correlation between HDL-C level and HDL-C peroxide content. Glucoregulation and inflammatory activity were assessed because both can be associated with dyslipidemia and HDL-C dysfunction. Obesity and central adiposity were also considered. Overall, women had healthier HDL-C profiles than men. Elevated HDL-C (>90 mg/dL) was common (16.6%) and found more often in women. Higher HDL-C peroxide content was associated with older age and central adiposity and incremented further when HA1c and CRP were higher. When assessed 5 years later, lower HDL-C peroxide content continued to be evident in adults with higher HDL-C. While similar associations have been described for other populations, most Japanese adults typically had healthier levels of HDL-C with lower HDL-C peroxide content than previously reported for American adults. Full article

(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)

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15 pages, 3424 KiB

Open AccessArticle

Expressions of Immune Prophenoloxidase (proPO) System-Related Genes Under Oxidative Stress in the Gonads and Stomach of the Mud Crab (Macrophthalmus japonicus) Exposed to Endocrine-Disrupting Chemicals

by Ji-Hoon Kim, Kiyun Park, Won-Seok Kim and Ihn-Sil Kwak

Antioxidants 2024, 13(12), 1433; https://doi.org/10.3390/antiox13121433 - 21 Nov 2024

Abstract

Endocrine-disrupting chemicals (EDCs) significantly damage biological systems related to reproductive, neurological, and metabolic functions. Approximately 1000 chemicals are known to possess endocrine-acting properties, including bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP). This study primarily focuses on the potential effects of EDCs on the [...] Read more.

Endocrine-disrupting chemicals (EDCs) significantly damage biological systems related to reproductive, neurological, and metabolic functions. Approximately 1000 chemicals are known to possess endocrine-acting properties, including bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP). This study primarily focuses on the potential effects of EDCs on the transcriptional levels of innate immune prophenoloxidase (proPO) system-related genes under oxidative stress in the gonads and stomach of the mud crab Macrophthalmus japonicus, an indicator species for assessing coastal benthic environments, when exposed to 1 µg L⁻¹, 10 µg L⁻¹, and 30 µg L⁻¹ BPA or DEHP. After EDC exposure, the expression of lipopolysaccharide and β-1,3-glucan-binding protein (LGBP), a pattern recognition protein that activates the proPO system, was upregulated in the stomach of M. japonicus, whereas LGBP gene expression was downregulated in the gonads. In the gonads, which is a reproductive organ, EDC exposure mainly induced the transcriptional upregulation of trypsin-like serine protease (Tryp) at relatively low concentrations. In the stomach, which is a digestive organ, LGBP expression was upregulated at relatively low concentrations of EDCs over 7 days, whereas all proPO system-related genes (LGBP, Tryp, serine protease inhibitor (Serpin), and peroxinectin (PE)) responded to all concentrations of EDCs. These results suggest that the antioxidant and immune defense responses of the proPO system to EDC toxicity may vary, causing different degrees of damage depending on the tissue type in the mud crab. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Environmental Toxicity)

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21 pages, 7859 KiB

Open AccessArticle

Flavonoid Fisetin Alleviates Ovarian Aging of Laying Chickens by Enhancing Antioxidant Capacity and Glucose Metabolic Homeostasis

by Zhaoyu Yang, Jiaxuan Zhang, Qiongyu Yuan, Xinyu Wang, Weidong Zeng, Yuling Mi and Caiqiao Zhang

Antioxidants 2024, 13(12), 1432; https://doi.org/10.3390/antiox13121432 - 21 Nov 2024

Abstract

Oxidative stress is a crucial factor contributing to ovarian follicular atresia and an imbalance in ovarian energy metabolism in poultry, leading to decreased laying performance in aging hens. This study aimed to investigate the effects of a natural flavonoid, fisetin, on laying performance, [...] Read more.

Oxidative stress is a crucial factor contributing to ovarian follicular atresia and an imbalance in ovarian energy metabolism in poultry, leading to decreased laying performance in aging hens. This study aimed to investigate the effects of a natural flavonoid, fisetin, on laying performance, ovarian redox status, and energy metabolism in laying chickens. The results showed that dietary fisetin supplementation improved egg production and eggshell quality in aging laying chickens, reduced follicular atresia rate, promoted ovarian cell proliferation, elevated serum estrogen and progesterone levels, restored ovarian antioxidant capacity, and improved energy metabolism. Furthermore, fisetin treatment increased the activity of antioxidant enzymes by inhibiting NF-κB signaling and COX-2 expression while promoting SIRT1 expression in the H₂O₂-induced small white follicle (SWF). Additionally, fisetin significantly enhanced the anti-apoptotic capacity of SWF and promoted glucose catabolism by activating the AKT and JNK signaling pathways. In summary, fisetin supplementation can alleviate ovarian oxidative stress in aging laying chickens by upregulating SIRT1 expression and inhibiting NF-κB signaling. The activation of AKT and JNK signaling pathways by fisetin contributes to the balance of energy metabolism and promotion of follicular development in the ovaries of aging laying chickens, thereby retarding ovarian aging in poultry production. Full article

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17 pages, 4383 KiB

Open AccessArticle

Thiol-Based Redox Molecules: Potential Antidotes for Acrylamide Toxicity

by Valeria Martin, Michael Trus and Daphne Atlas

Antioxidants 2024, 13(12), 1431; https://doi.org/10.3390/antiox13121431 - 21 Nov 2024

Abstract

Acrylamide (ACR) is a low-molecular weight, non-aromatic reagent, widely used in industry, such as in the manufacture of paper, textiles, plastics, cosmetics, and dyes. ACR is formed during the cooking of starchy food and its toxicity results mainly by conferring oxidative stress by [...] Read more.

Acrylamide (ACR) is a low-molecular weight, non-aromatic reagent, widely used in industry, such as in the manufacture of paper, textiles, plastics, cosmetics, and dyes. ACR is formed during the cooking of starchy food and its toxicity results mainly by conferring oxidative stress by elevating reactive oxygen species (ROS). To identify potential antidotes for ACR toxicity, we evaluated the efficacy of several thiol-based molecules known for ROS-scavenging, disulfide-reducing properties, and inhibition of oxidative stress-induced activation of the mitogen-activated protein kinases (MAPKs): the extracellular-signal-regulated-kinases (ERK1/2), p38-mitogen-activated-protein-kinases (p38^MAPK), and c-Jun-N-terminal-kinases (JNKs). We established a reproducible assay testing N-acetylcysteine (NAC), AD4/NACA, and the N-and C-blocked tri- and tetra-thioredoxin-mimetic (TXM) peptides, in PC12 cells. Our results demonstrate that these compounds exhibited high efficacy in suppressing ACR-induced MAPK activation, either prior to or subsequent to ACR exposure. The inhibition by single cysteine (Cys) residue, NAC and AD4/NACA (NAC-amide), 2 Cys peptides TXM-CB30, AcDCys-Gly-DCysNH₂, TXM-CB20, AcCys-Gly-CysNH₂, SuperDopa (SD, Ac-CysL-Levodopa-CysNH₂, TXM-CB13, AcCys-Met-Lys-CysNH₂, and a 3-Cys peptide, TXM-CB16, AcCys-γGlu-Cys-CysNH₂ was dose-dependent and potency displayed a direct correlation with the number of Cys residues. Cellular proteolysis of SD, which consists of levodopa flanked by two Cys, may suppress the manifestation of Parkinson’s disease (PD)-like symptoms mediated by chronic ACR exposure not only through lowering oxidative stress but also by replenishing cellular levels of dopamine. Overall, these results could advance the clinical application of TXM peptides as potential treatments for acute and/or chronic exposure to ACR and show promise as antidotes for preventing ACR-triggered PD-like neurotoxic symptoms. Full article

(This article belongs to the Section ROS, RNS and RSS)

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16 pages, 1875 KiB

Open AccessArticle

Initial Glutathione Depletion During Short-Term Bed Rest: Pinpointing Synthesis and Degradation Checkpoints in the γ-Glutamyl Cycle

by Filippo Giorgio Di Girolamo, Filippo Mearelli, Mariella Sturma, Nicola Fiotti, Kaja Teraž, Alja Ivetac, Alessio Nunnari, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot and Gianni Biolo

Antioxidants 2024, 13(12), 1430; https://doi.org/10.3390/antiox13121430 - 21 Nov 2024

Abstract

Hypokinesia triggers oxidative stress and accelerates the turnover of the glutathione system via the γ-glutamyl cycle. Our study aimed to identify the regulatory checkpoints controlling intracellular glutathione levels. We measured the intermediate substrates of the γ-glutamyl cycle in erythrocytes from 19 healthy young [...] Read more.

Hypokinesia triggers oxidative stress and accelerates the turnover of the glutathione system via the γ-glutamyl cycle. Our study aimed to identify the regulatory checkpoints controlling intracellular glutathione levels. We measured the intermediate substrates of the γ-glutamyl cycle in erythrocytes from 19 healthy young male volunteers before and during a 10-day experimental bed rest. Additionally, we tracked changes in glutathione levels and specific metabolite ratios up to 21 days of bed rest. Using gas chromatography-mass spectrometry and the internal standard technique, we observed a 9 ± 9% decrease in glutathione levels during the first 5 days of bed rest, followed by an 11 ± 9% increase from the 5th to the 10th day, nearly returning to baseline ambulatory levels. The cysteinyl-glycine-to-glutathione ratio, reflecting γ-glutamyl cyclotransferase activity (a key enzyme in glutathione breakdown), rose by 14 ± 22% in the first 5 days and then fell by 10 ± 14% over the subsequent 5 days, again approaching baseline levels. Additionally, the γ-glutamyl cysteine-to-cysteine ratio, indicative of γ-glutamyl cysteine synthetase activity (crucial for glutathione synthesis), increased by 12 ± 30% on day 5 and by 29 ± 41% on day 10 of bed rest. The results observed on day 21 of bed rest confirm those seen on day 10. By calculating the ratio of product concentration to precursor concentration, we assessed the efficiency of these key enzymes in glutathione turnover. These results were corroborated by directly measuring glutathione synthesis and degradation rates in vivo using stable isotope techniques. Our findings reveal significant changes in glutathione kinetics during the initial days of bed rest and identify potential therapeutic targets for maintaining glutathione levels. Full article

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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

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

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

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

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

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

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

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

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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