Antioxidants

19 pages, 1562 KiB

Open AccessReview

Antioxidant Functions of Vitamin D and CYP11A1-Derived Vitamin D, Tachysterol, and Lumisterol Metabolites: Mechanisms, Clinical Implications, and Future Directions

by Héctor Vázquez-Lorente, Lourdes Herrera-Quintana, Laura Jiménez-Sánchez, Beatriz Fernández-Perea and Julio Plaza-Diaz

Antioxidants 2024, 13(8), 996; https://doi.org/10.3390/antiox13080996 (registering DOI) - 17 Aug 2024

Abstract

Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as [...] Read more.

Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as improved immune, cardiovascular, and neurological functions as a result of chronic kidney disease and cancer. Additionally, supplementation with this vitamin has been shown to be one of the most cost-effective micronutrient interventions worldwide, highlighting its potential as a therapeutic approach. The underlying mechanisms and implications of this antioxidant function of vitamin D or CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites are not well understood. This comprehensive and narrative review is aimed at summarizing the current evidence regarding the molecular mechanisms implicated in this antioxidant function of vitamin D, as well as to provide a general overview and to identify key research areas for the future, offering an extensive perspective that can guide both researchers and clinicians in the management of diseases associated with oxidative stress and/or insufficient vitamin D status. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

15 pages, 2066 KiB

Open AccessArticle

A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing

by Joyce Ruifen Chong, Chiara de Lucia, Diego Alejandro Tovar-Rios, Nicolas Castellanos-Perilla, Christopher Collins, Silje Meihack Kvernberg, Clive Ballard, Richard C. Siow and Dag Aarsland

Antioxidants 2024, 13(8), 995; https://doi.org/10.3390/antiox13080995 (registering DOI) - 17 Aug 2024

Abstract

DailyColors™ is a supplement made up of several phytonutrients that aims to replicate elements from the Mediterranean diet. These include fruit, berry and vegetable extracts that are rich in key phytochemicals such as Quercetin, Catechins, Phloretin, Ellagic Acid, and Anthocyanins. Here, we determined [...] Read more.

DailyColors™ is a supplement made up of several phytonutrients that aims to replicate elements from the Mediterranean diet. These include fruit, berry and vegetable extracts that are rich in key phytochemicals such as Quercetin, Catechins, Phloretin, Ellagic Acid, and Anthocyanins. Here, we determined the effects of DailyColors™ on the blood biomarkers associated with the diverse mechanisms implicated in ageing and age-related diseases, including mitochondrial function, inflammation, and oxidative stress, as well as on saliva’s DNA methylation pattern. Thirty adult participants (mean (SD) age = 67.0 (7.5) years) with a body mass index over 25 were recruited into this randomised, double-blind, placebo-controlled, cross-over trial (two one-week treatment periods, separated by a one-week washout period). During the placebo period, we observed a significant increase in blood CD38 concentrations from the baseline to 24 h (p-value = 0.019). This was not observed in the active period. Increased CD38 is reportedly associated with subsequent mitochondrial dysfunction and inflammation. Next, there was a decreasing trend of plasma 4-HNE levels, an oxidative stress biomarker, after a one-week intake of DailyColors™. Furthermore, following a one-month open-label follow-up in 26 participants, we observed hypermethylation of the candidate CpG site cg13108341 (q-value = 0.021), which was against the observed trend for this site during ageing. Taken together, while minimal effects were observed in this study, DailyColors™ supplementation may be beneficial by altering and alleviating age-related changes. Longer and larger scale trials of DailyColors™ supplementation are warranted. Full article

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15 pages, 1858 KiB

Open AccessArticle

Biochemical Characterization of New Sweet Orange Mutants Rich in Lycopene and β-Carotene Antioxidants

by Lourdes Carmona, Berta Alquézar and Leandro Peña

Antioxidants 2024, 13(8), 994; https://doi.org/10.3390/antiox13080994 - 16 Aug 2024

Abstract

Carotenoid-rich foods such as citrus fruits have a wide range of functions in human health. They primarily exert antioxidant effects, but individual carotenoids may also act through other health-promoting mechanisms such as β-carotene as pro-vitamin A. Here, we show that red-fleshed sweet oranges [...] Read more.

Carotenoid-rich foods such as citrus fruits have a wide range of functions in human health. They primarily exert antioxidant effects, but individual carotenoids may also act through other health-promoting mechanisms such as β-carotene as pro-vitamin A. Here, we show that red-fleshed sweet oranges grown in tropical climates are 4–9 times richer in carotenoids than their orange-fleshed counterparts, regardless of their maturation stage. The most significant difference observed between both varieties was the presence of lycopene at moderate concentrations (around 8 µg/g FW) in the mature pulp of the red varieties, which was absent in the blond ones. This is because the red-fleshed sweet oranges grown in tropical climates with high temperatures increase lycopene and β-carotene concentrations in their pulp during fruit maturation. Due to lycopene accumulation, red orange juice offers a promising addition to popular blond-orange, with the new varieties Carrancas and Pinhal being perfectly suitable for blending to enhance juice colour. Sao Paulo, one of the world’s leading citrus orange juice producers, as well as other tropical citrus regions could benefit from cultivating using such lycopene-rich cultivars and industrially. 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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16 pages, 436 KiB

Open AccessArticle

Characterization of Phenolic Profile and Biological Properties of Astragalus membranaceus Fisch. ex Bunge Commercial Samples

by Saba Shahrivari-Baviloliaei, Ilkay Erdogan Orhan, Nurten Abaci Kaplan, Agnieszka Konopacka, Krzysztof Waleron, Alina Plenis and Agnieszka Viapiana

Antioxidants 2024, 13(8), 993; https://doi.org/10.3390/antiox13080993 - 16 Aug 2024

Abstract

Astragalus membranaceus Fisch. ex Bunge (syn. Astragalus mongholicus Bunge) is one of the notable medicinal and food plants. Therefore, the aim of this study was to calculate the phenolic composition and antioxidant, antimicrobial, as well as enzyme inhibitory [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and [...] Read more.

Astragalus membranaceus Fisch. ex Bunge (syn. Astragalus mongholicus Bunge) is one of the notable medicinal and food plants. Therefore, the aim of this study was to calculate the phenolic composition and antioxidant, antimicrobial, as well as enzyme inhibitory [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR)] activities with chemometric approaches of the hydromethanolic and water extracts of commercial A. membranaceus samples. Ten individual phenolic compounds were determined using high-performance liquid chromatography (HPLC), and only quercetin was found at a level of above 80 µg/g DW in both extracts. Moreover, the highest antioxidant activity in DPPH, FRAP, ABTS, and CUPRAC assays was found in the sample containing the roots in loose form from USA. A. membranaceus extracts displayed the inhibition zone diameters within the range from 10 to 22 mm antimicrobial activity against S. aureus, while there were no inhibition zones in any extracts in case of E. coli. The extracts of A. membranaceous showed an inhibition rate below 40% against TYR, and among tested extracts, only two samples were able to inhibit BChE with IC₅₀ values of above 30 µg/mL. Correlation analysis showed a highly positive relationship between their phenolic composition and antioxidant activity. Concluding, the obtained results confirmed that A. membranaceus commercial samples could be an important dietary source of natural antioxidants. 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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22 pages, 2988 KiB

Open AccessReview

From Waste to Wealth: Exploring the Bioactive Potential of Wine By-Products—A Review

by Glenda-Caridad Peña-Portillo, Sergio-Miguel Acuña-Nelson and José-Miguel Bastías-Montes

Antioxidants 2024, 13(8), 992; https://doi.org/10.3390/antiox13080992 - 15 Aug 2024

Abstract

The present paper explores the biological potential of bioactive compounds present in wine industry wastes, highlighting their valorization to promote sustainability and circular economy. Wine by-products, such as grape pomace and vine shoots, contain a high concentration of polyphenols, flavonoids, anthocyanins and other [...] Read more.

The present paper explores the biological potential of bioactive compounds present in wine industry wastes, highlighting their valorization to promote sustainability and circular economy. Wine by-products, such as grape pomace and vine shoots, contain a high concentration of polyphenols, flavonoids, anthocyanins and other phytochemicals with antioxidant, anti-inflammatory and anticarcinogenic properties. Both conventional extraction methods, such as solid–liquid extraction, and emerging technologies, including enzyme-assisted extraction, ultrasound-assisted extraction, supercritical fluid extraction, microwave-assisted extraction, pressurized liquid extraction, high-hydrostatic-pressure extraction, and deep natural solvent-assisted extraction (NaDES), are discussed. In addition, the preservation of polyphenolic extracts by microencapsulation, a key technique to improve the stability and bioavailability of bioactive compounds, is addressed. The combination of advanced extraction methods and innovative preservation techniques offers a promising perspective for the valorization of bioactive compounds from wine residues, driving sustainability and innovation in the industry. Full article

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

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17 pages, 2838 KiB

Open AccessArticle

The SOD1 Inhibitor, LCS-1, Oxidizes H2S to Reactive Sulfur Species, Directly and Indirectly, through Conversion of SOD1 to an Oxidase

by Kenneth R. Olson, Tsuyoshi Takata, Kasey J. Clear, Yan Gao, Zhilin Ma, Ella Pfaff, Karthik Mouli, Thomas A. Kent, Prentiss Jones, Jr., Jon Fukuto, Gang Wu and Karl D. Straub

Antioxidants 2024, 13(8), 991; https://doi.org/10.3390/antiox13080991 - 15 Aug 2024

Abstract

LCS-1, a putative selective inhibitor of SOD1, is a substituted pyridazinone with rudimentary similarity to quinones and naphthoquinones. As quinones catalytically oxidize H₂S to biologically active reactive sulfur species (RSS), we hypothesized LCS-1 might have similar attributes. Here, we examine LCS-1 [...] Read more.

LCS-1, a putative selective inhibitor of SOD1, is a substituted pyridazinone with rudimentary similarity to quinones and naphthoquinones. As quinones catalytically oxidize H₂S to biologically active reactive sulfur species (RSS), we hypothesized LCS-1 might have similar attributes. Here, we examine LCS-1 reactions with H₂S and SOD1 using thiol-specific fluorophores, liquid chromatography–mass spectrometry, electron paramagnetic resonance (EPR), UV–vis spectrometry, and oxygen consumption. We show that LCS-1 catalytically oxidizes H₂S in buffer solutions to form RSS, namely per- and polyhydrosulfides (H₂S_n, n = 2–6). These reactions consume oxygen and produce hydrogen peroxide, but they do not have an EPR signature, nor do they affect the UV–vis spectrum. Surprisingly, LCS-1 synergizes with SOD1, but not SOD2, to oxidize H₂S to H₂S_3-6. LCS-1 forms monothiol adducts with H₂S, glutathione (GSH), and cysteine (Cys), but not with oxidized glutathione or cystine; both thiol adducts inhibit LCS-1-SOD1 synergism. We propose that LCS-1 forms an adduct with SOD1 that disrupts the intramolecular Cys⁵⁷-Cys¹⁴⁶ disulfide bond and transforms SOD1 from a dismutase to an oxidase. This would increase cellular ROS and polysulfides, the latter potentially affecting cellular signaling and/or cytoprotection. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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14 pages, 1327 KiB

Open AccessArticle

Direct Molecular Action of Taurine on Hepatic Gene Expression Associated with the Amelioration of Hypercholesterolemia in Rats

by Qi Song, Satoru Kobayashi, Yutaro Kataoka and Hiroaki Oda

Antioxidants 2024, 13(8), 990; https://doi.org/10.3390/antiox13080990 - 14 Aug 2024

Abstract

Taurine can ameliorate hypercholesterolemia by facilitating cholesterol efflux and increasing cytochrome P450 7A1 (CYP7A1) without clear underlying molecular mechanisms. This study aims to elucidate the molecular action of taurine in diet-induced hypercholesterolemia. Male Wistar rats were fed a high cholesterol diet containing 5% [...] Read more.

Taurine can ameliorate hypercholesterolemia by facilitating cholesterol efflux and increasing cytochrome P450 7A1 (CYP7A1) without clear underlying molecular mechanisms. This study aims to elucidate the molecular action of taurine in diet-induced hypercholesterolemia. Male Wistar rats were fed a high cholesterol diet containing 5% taurine for 14 days. Three-dimensional primary hepatocytes from rats were exposed to 10 mM taurine for 24 h. Transcriptome analyses of both the liver and hepatocytes were performed using DNA microarray. Taurine significantly decreased serum cholesterol levels and increased hepatic CYP7A1 mRNA levels and transcription rates in rats. Taurine altered the expression of seventy-seven genes in the liver, involving lipid, drug, amino acid metabolism, and gluconeogenesis pathways. The small heterodimer partner (SHP), a transcription factor regulated by taurine, was suppressed. “Network analysis” revealed a negative correlation between the SHP and induction of CYP7A1 and cytochrome P450 8B1 (CYP8B1). However, CYP7A1 and CYP8B1 levels were not altered by taurine in 3D-primary hepatocytes. Venn diagram analyses of the transcriptomes in both hepatocytes and the liver indicated a consistent upregulation of organic anion transporting polypeptide 2 (OATP2) and betaine homocysteine methyltransferase (BHMT). Taurine ameliorated hypercholesterolemia in rats fed a high cholesterol diet by directly enhancing the hepatic expression of BHMT and OATP2, which modulated the SHP and induced CYP7A1 and CYP8B1, thereby promoting cholesterol catabolism and lowering blood cholesterol levels. Full article

(This article belongs to the Special Issue Cellular Sulfur Metabolism and Signaling in Physiology and Pathology)

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23 pages, 3750 KiB

Open AccessArticle

Physical Properties of Cellulose Derivative-Based Edible Films Elaborated with Liposomes Encapsulating Grape Seed Tannins

by Constanza Vidal, Johana Lopez-Polo and Fernando A. Osorio

Antioxidants 2024, 13(8), 989; https://doi.org/10.3390/antiox13080989 - 14 Aug 2024

Abstract

Combined use of edible films (EF) with nanoencapsulation systems could be an effective alternative for improving the films’ physical properties and maintaining bioactive compounds’ stability. This research work focuses on the combined use of EF of cellulose-derived biopolymers enriched with liposomes that encapsulate [...] Read more.

Combined use of edible films (EF) with nanoencapsulation systems could be an effective alternative for improving the films’ physical properties and maintaining bioactive compounds’ stability. This research work focuses on the combined use of EF of cellulose-derived biopolymers enriched with liposomes that encapsulate grape seed tannins and on the subsequent evaluation of the physical properties and wettability. Tannin-containing liposomal suspensions (TLS) showed 570.8 ± 6.0 nm particle size and 99% encapsulation efficiency. In vitro studies showed that the release of tannins from liposomes was slower than that of free tannins, reaching a maximum release of catechin of 0.13 ± 0.01%, epicatechin of 0.57 ± 0.01%, and gallic acid of 3.90 ± 0.001% over a 144 h period. Adding liposomes to biopolymer matrices resulted in significant decrease (p < 0.05) of density, surface tension, tensile strength, elongation percentage, and elastic modulus in comparison to the control, obtaining films with greater flexibility and lower breaking strength. Incorporating TLS into EF formulations resulted in partially wetting the hydrophobic surface, reducing adhesion and cohesion compared to EF without liposomes. Results indicate that the presence of liposomes improves films’ physical and wettability properties, causing them to extend and not contract when applied to hydrophobic food surfaces. Full article

(This article belongs to the Special Issue Green Extraction and Formulation of Antioxidants Derived from Food- and Agricultural Waste)

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19 pages, 4851 KiB

Open AccessArticle

Sea Cucumber Viscera Processed by Protease Hydrolysis Combined with Cordyceps militaris Fermentation Protect Caco-2 Cells against Oxidative Damage via Enhancing Antioxidant Capacity, Activating Nrf2/HO-1 Pathway and Improving Cell Metabolism

by Rui Mi, Zhiyu Fu, Jingwei Jiang, Shan Gao, Xiaoyan Guan, Xuda Wang and Zunchun Zhou

Antioxidants 2024, 13(8), 988; https://doi.org/10.3390/antiox13080988 - 14 Aug 2024

Abstract

Excessive reactive oxygen species (ROS) may lead to oxidative damage and metabolic disorder. The pathogenesis of human bowel inflammation is closely related to oxidative damage of intestinal epithelial cells caused by ROS. This study aimed to explore the high-value utilization of the byproducts [...] Read more.

Excessive reactive oxygen species (ROS) may lead to oxidative damage and metabolic disorder. The pathogenesis of human bowel inflammation is closely related to oxidative damage of intestinal epithelial cells caused by ROS. This study aimed to explore the high-value utilization of the byproducts of sea cucumber in antioxidant food for colitis prevention. The technology of protease hydrolysis combined with Cordyceps militaris fermentation was used to obtain fermented sea cucumber viscera protease hydrolysates (FSVHs). The results revealed that FSVH could enhance antioxidant capacity and alleviate oxidative damage and apoptosis by activating the Nrf2/HO-1 pathway and triggering the self-protection immune mechanisms. Moreover, the FSVH supplementation could upregulate antioxidant-related metabolic pathways of Caco-2 cells such as glutathione metabolism, confirming the enhanced antioxidant capacity of damaged cells. In summary, FSVH could exert protective effects on Caco-2 cells in response to oxidative damage, providing a promising prospect for sea cucumber resource utilization and colitis prevention. Full article

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3 pages, 204 KiB

Open AccessCorrection

Correction: Gómez et al. Long-Term Effect of Maternal Antioxidant Supplementation on the Lipid Profile of the Progeny According to the Sow’s Parity Number. Antioxidants 2024, 13, 379

by Gerardo Gómez, Hernan D. Laviano, Juan García-Casco, Maria Muñoz, Fernando Gómez, Fernando Sánchez-Esquiliche, Antonio González-Bulnes, Clemente López-Bote, Cristina Óvilo and Ana I. Rey

Antioxidants 2024, 13(8), 987; https://doi.org/10.3390/antiox13080987 - 14 Aug 2024

Abstract

In the original publication [...] Full article

16 pages, 3935 KiB

Open AccessArticle

Exploration of the Synergistic Regulation Mechanism in Cerebral Ganglion and Heart of Eriocheir sinensis on Energy Metabolism and Antioxidant Homeostasis Maintenance under Alkalinity Stress

by Meiyao Wang, Jun Zhou, Gangchun Xu and Yongkai Tang

Antioxidants 2024, 13(8), 986; https://doi.org/10.3390/antiox13080986 - 14 Aug 2024

Abstract

(1) The development and utilization of the vast saline–alkali land worldwide is an important way to solve the worsening food crisis. Eriocheir sinensis, due to its strong osmotic regulation capability and its characteristics of being suitable for culturing in alkaline water, has [...] Read more.

(1) The development and utilization of the vast saline–alkali land worldwide is an important way to solve the worsening food crisis. Eriocheir sinensis, due to its strong osmotic regulation capability and its characteristics of being suitable for culturing in alkaline water, has become a potential aquaculture species in saline–alkali water. The brain and heart are the key tissues for signal transduction and energy supply under environmental stress. (2) This study is the first to explore the synergistic regulatory molecular mechanism by integrated analysis on cerebral ganglion proteomics and heart metabolomics of Eriocheir sinensis under alkalinity stress. (3) The results indicate that the cerebral ganglion and heart of E. sinensis were closely related in response to acute alkalinity stress. The differential regulatory pathways mainly involved regulation of energy metabolism, amino acid metabolism, and homeostasis maintenance. Importantly, alkalinity stress induced the regulation of antioxidants and further adjusted longevity and rhythm in the cerebral ganglion and heart, reflecting that the cerebral ganglion and heart may be the key tissues for the survival of Eriocheir sinensis under an alkalinity environment. (4) This study provides a theoretical reference for research on the regulation mechanism of E. sinensis under alkalinity condition and contributes to the development of aquaculture in saline–alkali water. Full article

(This article belongs to the Special Issue Antioxidant Response in Aquatic Animals)

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20 pages, 779 KiB

Open AccessReview

Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases

by Hamid Mostafavi Abdolmaleky and Jin-Rong Zhou

Antioxidants 2024, 13(8), 985; https://doi.org/10.3390/antiox13080985 - 14 Aug 2024

Abstract

Gut dysbiosis, resulting from an imbalance in the gut microbiome, can induce excessive production of reactive oxygen species (ROS), leading to inflammation, DNA damage, activation of the immune system, and epigenetic alterations of critical genes involved in the metabolic pathways. Gut dysbiosis-induced inflammation [...] Read more.

Gut dysbiosis, resulting from an imbalance in the gut microbiome, can induce excessive production of reactive oxygen species (ROS), leading to inflammation, DNA damage, activation of the immune system, and epigenetic alterations of critical genes involved in the metabolic pathways. Gut dysbiosis-induced inflammation can also disrupt the gut barrier integrity and increase intestinal permeability, which allows gut-derived toxic products to enter the liver and systemic circulation, further triggering oxidative stress, inflammation, and epigenetic alterations associated with metabolic diseases. However, specific gut-derived metabolites, such as short-chain fatty acids (SCFAs), lactate, and vitamins, can modulate oxidative stress and the immune system through epigenetic mechanisms, thereby improving metabolic function. Gut microbiota and diet-induced metabolic diseases, such as obesity, insulin resistance, dyslipidemia, and hypertension, can transfer to the next generation, involving epigenetic mechanisms. In this review, we will introduce the key epigenetic alterations that, along with gut dysbiosis and ROS, are engaged in developing metabolic diseases. Finally, we will discuss potential therapeutic interventions such as dietary modifications, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, which may reduce oxidative stress and inflammation associated with metabolic syndrome by altering gut microbiota and epigenetic alterations. In summary, this review highlights the crucial role of gut microbiota dysbiosis, oxidative stress, and inflammation in the pathogenesis of metabolic diseases, with a particular focus on epigenetic alterations (including histone modifications, DNA methylomics, and RNA interference) and potential interventions that may prevent or improve metabolic diseases. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic Syndrome: The Role of Gut Microbiota)

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19 pages, 4594 KiB

Open AccessArticle

Resveratrol Mitigates Cognitive Impairments and Cholinergic Cell Loss in the Medial Septum in a Mouse Model of Gradual Cerebral Hypoperfusion

by Eric Fagerli, Charles W. Jackson, Iris Escobar, Fernando J. Ferrier, Efrain J. Perez Lao, Isabel Saul, Jorge Gomez, Kunjan R. Dave, Oliver Bracko and Miguel A. Perez-Pinzon

Antioxidants 2024, 13(8), 984; https://doi.org/10.3390/antiox13080984 - 14 Aug 2024

Abstract

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia. There is currently no effective treatment for VCID. Resveratrol (RSV) is considered an antioxidant; however, our group has observed pleiotropic effects in stroke paradigms, suggesting more effects may contribute to [...] Read more.

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia. There is currently no effective treatment for VCID. Resveratrol (RSV) is considered an antioxidant; however, our group has observed pleiotropic effects in stroke paradigms, suggesting more effects may contribute to mechanistic changes beyond antioxidative properties. The main goal of this study was to investigate if administering RSV twice a week could alleviate cognitive declines following the induction of a VCID model. Additionally, our aim was to further describe whether this treatment regimen could decrease cell death in brain areas vulnerable to changes in cerebral blood flow, such as the hippocampus and medial septum. We hypothesized RSV treatments in a mouse model of gradual cerebral hypoperfusion protect against cognitive impairment. We utilized gradual bilateral common carotid artery stenosis (GBCCAS) via the surgical implantation of ameroid constrictor devices. RSV treatment was administered on the day of implantation and twice a week thereafter. Cerebral perfusion was measured by laser speckle contrast imaging, and cognitive functions, including the recognition memory, the spatial working memory, and associative learning, were assessed by novel object recognition (NOR), Y-maze testing, and contextual fear conditioning (CFC), respectively. RSV treatment did not alleviate cerebral perfusion deficits but mitigated cognitive deficits in CFC and NOR after GBCCAS. Despite these deficits, no hippocampal pathology was observed; however, cholinergic cell loss in the medial septum was significantly increased after GBCCAS. This cholinergic cell loss was mitigated by RSV. This study describes a novel mechanism by which chronic RSV treatments protect against a VCID-induced cognitive decline through the preservation of cholinergic cell viability to improve memory performance. Full article

(This article belongs to the Special Issue Oxidative Stress and Pathophysiology of Stroke)

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13 pages, 808 KiB

Open AccessArticle

Curcumin Supplementation and Vascular and Cognitive Function in Chronic Kidney Disease: A Randomized Controlled Trial

by Colin J. Gimblet, Nicholas T. Kruse, Katharine Geasland, Jeni Michelson, Mingyao Sun, Patrick Ten Eyck, Cari Linkenmeyer, Safur Rehman Mandukhail, Matthew J. Rossman, Meenakshi Sambharia, Michel Chonchol, Manjula Kurella Tamura, Douglas Seals, Karin F. Hoth and Diana Jalal

Antioxidants 2024, 13(8), 983; https://doi.org/10.3390/antiox13080983 - 14 Aug 2024

Abstract

Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that [...] Read more.

Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida^®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid–femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was −0.7 (−2.1, 1.1) and −0.1 (−1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD. Full article

(This article belongs to the Special Issue Oxidative Stress in Renal Health)

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17 pages, 3891 KiB

Open AccessArticle

Protective Effects of 7S,15R-Dihydroxy-16S,17S-Epoxy-Docosapentaenoic Acid (diHEP-DPA) against Blue Light-Induced Retinal Damages in A2E-Laden ARPE-19 Cells

by Seung-Yub Song, Dae-Hun Park, Sung-Ho Lee, Han-Kyu Lim, Jin-Woo Park, Jeong-Woo Seo and Seung-Sik Cho

Antioxidants 2024, 13(8), 982; https://doi.org/10.3390/antiox13080982 - 13 Aug 2024

Abstract

The purpose of this study was to investigate the protective effects of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) in retinal pigment epithelial (RPE) cell damage. ARPE-19 cells, a human RPE cell line, were cultured with diHEP-DPA and Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), followed by exposure to BL. [...] Read more.

The purpose of this study was to investigate the protective effects of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) in retinal pigment epithelial (RPE) cell damage. ARPE-19 cells, a human RPE cell line, were cultured with diHEP-DPA and Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), followed by exposure to BL. Cell viability and cell death rates were determined. Western blotting was performed to determine changes in apoptotic factors, mitogen-activated protein kinase (MAPK) family proteins, inflammatory proteins, and oxidative and carbonyl stresses. The levels of pro-inflammatory cytokines in the culture medium supernatants were also measured. Exposure to A2E and BL increased the ARPE-19 cell death rate, which was alleviated by diHEP-DPA in a concentration-dependent manner. A2E and BL treatments induced apoptosis in ARPE-19 cells, which was also alleviated by diHEP-DPA. Analysis of the relationship with MAPK proteins revealed that the expression of p-JNK and p-P38 increased after A2E and BL treatments and decreased with exposure to diHEP-DPA in a concentration-dependent manner. DiHEP-DPA also affected the inflammatory response by suppressing the expression of inflammatory proteins and the production of pro-inflammatory cytokines. Furthermore, it was shown that diHEP-DPA regulated the proteins related to oxidative and carbonyl stresses. Taken together, our results provide evidence that diHEP-DPA can inhibit cell damage caused by A2E and BL exposure at the cellular level by controlling various pathways involved in apoptosis and inflammatory responses. Full article

(This article belongs to the Special Issue Cellular Responses of Antioxidants Related to Degenerative Eye Disease Research)

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19 pages, 6169 KiB

Open AccessArticle

The Antioxidant and Anti-Inflammatory Properties of Bee Pollen from Acorn (Quercus acutissima Carr.) and Darae (Actinidia arguta)

by Jeong-Eun Kwak, Joo-Yeon Lee, Ji-Yoon Baek, Sun Wook Kim and Mok-Ryeon Ahn

Antioxidants 2024, 13(8), 981; https://doi.org/10.3390/antiox13080981 - 13 Aug 2024

Abstract

Aging is a complex biological process characterized by a progressive decline in physical function and an increased risk of age-related chronic diseases. Additionally, oxidative stress is known to cause severe tissue damage and inflammation. Pollens from acorn and darae are extensively produced in [...] Read more.

Aging is a complex biological process characterized by a progressive decline in physical function and an increased risk of age-related chronic diseases. Additionally, oxidative stress is known to cause severe tissue damage and inflammation. Pollens from acorn and darae are extensively produced in Korea. However, the underlying molecular mechanisms of these components under the conditions of inflammation and oxidative stress remain largely unknown. This study aimed to investigate the effect of bee pollen components on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages. This study demonstrates that acorn and darae significantly inhibit the LPS-induced production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), in RAW 264.7 cells. Specifically, bee pollen from acorn reduces NO production by 69.23 ± 0.04% and PGE2 production by 44.16 ± 0.08%, while bee pollen from darae decreases NO production by 78.21 ± 0.06% and PGE2 production by 66.23 ± 0.1%. Furthermore, bee pollen from acorn and darae reduced active oxygen species (ROS) production by 47.01 ± 0.5% and 60 ± 0.9%, respectively. It increased the nuclear potential of nuclear factor erythroid 2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 cells. Moreover, treatment with acorn and darae abolished the nuclear potential of nuclear factor κB (NF-κB) and reduced the expression of extracellular signal-associated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation in LPS-stimulated RAW 264.7 cells. Specifically, acorn decreased NF-κB nuclear potential by 90.01 ± 0.3%, ERK phosphorylation by 76.19 ± 1.1%, and JNK phosphorylation by 57.14 ± 1.2%. Similarly, darae reduced NF-κB nuclear potential by 92.21 ± 0.5%, ERK phosphorylation by 61.11 ± 0.8%, and JNK phosphorylation by 59.72 ± 1.12%. These results suggest that acorn and darae could be potential antioxidants and anti-inflammatory agents. Full article

(This article belongs to the Special Issue Bee Products as a Source of Natural Antioxidants: Second Edition)

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15 pages, 4910 KiB

Open AccessArticle

Mechanism of Mitochondrial Kinetic Imbalance and Nrf2 Signaling Pathway-Mediated Oxidative Stress in Nickel and/or Chromium-Induced Kidney Injury in Mice

by Jun Du, Zhengqing Li, Xianhong Cao, Qiurong Qi, Luqi Wang, Ping Liu, Yifei Chen, Guoliang Hu, Xiaoquan Guo and Xiaona Gao

Antioxidants 2024, 13(8), 980; https://doi.org/10.3390/antiox13080980 - 13 Aug 2024

Abstract

Nickel and chromium are both common heavy metals that pose serious environmental and health hazards. However, the exact mechanism by which nickel and/or chromium cause renal injury is unclear. Therefore, we explored the molecular mechanisms of renal injury caused by nickel and/or chromium [...] Read more.

Nickel and chromium are both common heavy metals that pose serious environmental and health hazards. However, the exact mechanism by which nickel and/or chromium cause renal injury is unclear. Therefore, we explored the molecular mechanisms of renal injury caused by nickel and/or chromium poisoning from the perspective of mitochondrial dynamics and the Nrf2 antioxidant pathway. In this study, eighty 6-week-old C57BL/6J mice were randomly divided into four groups: control (Con, untreated), nickel (Ni, 110 mg/L Ni²⁺), chromium (Cr, 50 mg/L Cr⁶⁺), and combined nickel–chromium (Ni + Cr, 110 mg/L Ni²⁺, 50 mg/L Cr⁶⁺). The results showed that chronic nickel and/or chromium exposure inhibited body weight gain and impaired kidney function and structure in mice. Chronic nickel and/or chromium exposure led to the disruption of mitochondrial dynamics and thus induced oxidative stress. On the other hand, the Nrf2 antioxidant pathway may play an important regulatory role in mitigating oxidative stress-induced oxidative damage in kidney. The present study partially elucidated the molecular mechanism of renal injury induced by nickel and/or chromium exposure in mice and the regulatory role of the Nrf2 pathway in inducing oxidative injury from the perspective of mitochondrial dynamics. This provides a theoretical basis for the development of prevention and control strategies, and environmental protection measures. Full article

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22 pages, 3341 KiB

Open AccessReview

Pregnancy Disorders: A Potential Role for Mitochondrial Altered Homeostasis

by Juan M. Toledano, María Puche-Juarez, Jose Maria Galvez-Navas, Jorge Moreno-Fernandez, Javier Diaz-Castro and Julio J. Ochoa

Antioxidants 2024, 13(8), 979; https://doi.org/10.3390/antiox13080979 - 13 Aug 2024

Abstract

Pregnancy is a complex and challenging process associated with physiological changes whose objective is to adapt the maternal organism to the increasing energetic requirements due to embryo and fetal development. A failed adaptation to these demands may lead to pregnancy complications that threaten [...] Read more.

Pregnancy is a complex and challenging process associated with physiological changes whose objective is to adapt the maternal organism to the increasing energetic requirements due to embryo and fetal development. A failed adaptation to these demands may lead to pregnancy complications that threaten the health of both mothers and their offspring. Since mitochondria are the main organelle responsible for energy generation in the form of ATP, the adequate state of these organelles seems crucial for proper pregnancy development and healthy pregnancy outcomes. The homeostasis of these organelles depends on several aspects, including their content, biogenesis, energy production, oxidative stress, dynamics, and signaling functions, such as apoptosis, which can be modified in relation to diseases during pregnancy. The etiology of pregnancy disorders like preeclampsia, fetal growth restriction, and gestational diabetes mellitus is not yet well understood. Nevertheless, insufficient placental perfusion and oxygen transfer are characteristic of many of them, being associated with alterations in the previously cited different aspects of mitochondrial homeostasis. Therefore, and due to the capacity of these multifactorial organelles to respond to physiological and pathophysiological stimuli, it is of great importance to gather the currently available scientific information regarding the relationship between main pregnancy complications and mitochondrial alterations. According to this, the present review is intended to show clear insight into the possible implications of mitochondria in these disorders, thus providing relevant information for further investigation in relation to the investigation and management of pregnancy diseases. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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25 pages, 7480 KiB

Open AccessArticle

Heavy Metal Exposure-Mediated Dysregulation of Sphingolipid Metabolism

by Shaheer Ahmad, Sierra Single, Yuelong Liu, Kenneth P. Hough, Yong Wang, Victor J. Thannickal, Mohammad Athar, Kayla F. Goliwas and Jessy S. Deshane

Antioxidants 2024, 13(8), 978; https://doi.org/10.3390/antiox13080978 - 12 Aug 2024

Abstract

Exposure to heavy metals (HMs) is often associated with inflammation and cell death, exacerbating respiratory diseases including asthma. Most inhaled particulate HM exposures result in the deposition of HM-bound fine particulate matter, PM_2.5, in pulmonary cell populations. While localized high concentrations [...] Read more.

Exposure to heavy metals (HMs) is often associated with inflammation and cell death, exacerbating respiratory diseases including asthma. Most inhaled particulate HM exposures result in the deposition of HM-bound fine particulate matter, PM_2.5, in pulmonary cell populations. While localized high concentrations of HMs may be a causative factor, existing studies have mostly evaluated the effects of systemic or low-dose chronic HM exposures. This report investigates the impact of local high concentrations of specific HMs (NaAsO₂, MnCl₂, and CdCl₂) on sphingolipid homeostasis and oxidative stress, as both play a role in mediating responses to HM exposure and have been implicated in asthma. Utilizing an in vitro model system and three-dimensional ex vivo human tissue models, we evaluated the expression of enzymatic regulators of the salvage, recycling, and de novo synthesis pathways of sphingolipid metabolism, and observed differential modulation in these enzymes between HM exposures. Sphingolipidomic analyses of specific HM-exposed cells showed increased levels of anti-apoptotic sphingolipids and reduced pro-apoptotic sphingolipids, suggesting activation of the salvage and de novo synthesis pathways. Differential sphingolipid regulation was observed within HM-exposed lung tissues, with CdCl₂ exposure and NaAsO₂ exposure activating the salvage and de novo synthesis pathway, respectively. Additionally, using spatial transcriptomics and quantitative real-time PCR, we identified HM exposure-induced transcriptomic signatures of oxidative stress in epithelial cells and human lung tissues. Full article

(This article belongs to the Special Issue Oxidative Stress and Environmental Toxicology)

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