Antioxidants

31 pages, 673 KiB

Open AccessReview

Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy—A State-of-the-Art Review

by Olaf Rose, Tim Croonenberg, Stephanie Clemens, Tobias Hinteregger, Stefanie Eppacher, Petra Huber-Cantonati, Marta Garcia-Miralles, Raffaella Liuni and Silvia Dossena

Antioxidants 2024, 13(12), 1578; https://doi.org/10.3390/antiox13121578 (registering DOI) - 21 Dec 2024

Abstract

Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential for serious adverse effects. Ototoxicity from cisplatin treatment is an important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, [...] Read more.

Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential for serious adverse effects. Ototoxicity from cisplatin treatment is an important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, and vestibular dysfunction. Despite the recent approval of sodium thiosulphate for the prevention of cisplatin-induced hearing loss (CIHL) in pediatric patients, structured prevention programs are not routinely implemented in most hospitals, and reducing platinum-induced ototoxicity in adults remains an important clinical problem without established treatment options. Cochlear oxidative stress plays a fundamental role in CIHL. Here, we review the molecular mechanisms leading to oxidative stress in CIHL and the clinical and preclinical studies testing antioxidants in CIHL to guide future clinical trials in assessing the efficacy and safety of candidate antioxidant compounds in this clinical setting. Full article

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

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19 pages, 2030 KiB

Open AccessArticle

First Characterization of Cyanobacterial Xi-Class Glutathione S-Transferase in Synechocystis PCC 6803

by Fanny Marceau, Marlène Lamothe-Sibold, Sandrine Farci, Soufian Ouchane, Corinne Cassier-Chauvat and Franck Chauvat

Antioxidants 2024, 13(12), 1577; https://doi.org/10.3390/antiox13121577 (registering DOI) - 20 Dec 2024

Abstract

Glutathione S-transferases (GSTs) are evolutionarily conserved enzymes crucial for cell detoxication. They are viewed as having evolved in cyanobacteria, the ancient photosynthetic prokaryotes that colonize our planet and play a crucial role for its biosphere. Xi-class GSTs, characterized by their specific glutathionyl–hydroquinone reductase [...] Read more.

Glutathione S-transferases (GSTs) are evolutionarily conserved enzymes crucial for cell detoxication. They are viewed as having evolved in cyanobacteria, the ancient photosynthetic prokaryotes that colonize our planet and play a crucial role for its biosphere. Xi-class GSTs, characterized by their specific glutathionyl–hydroquinone reductase activity, have been observed in prokaryotes, fungi and plants, but have not yet been studied in cyanobacteria. In this study, we have analyzed the presumptive Xi-class GST, designated as Slr0605, of the unicellular model cyanobacterium Synechocystis PCC 6803. We report that Slr0605 is a homodimeric protein that has genuine glutathionyl–hydroquinone reductase activity. Though Slr0605 is not essential for cell growth under standard photoautotrophic conditions, it plays a prominent role in the protection against not only benzoquinone, but also cobalt-excess stress. Indeed, Slr0605 acts in defense against the cobalt-elicited disturbances of iron homeostasis, iron–sulfur cluster repair, catalase activity and the level of reactive oxygen species, which are all crucial for cell life. Full article

(This article belongs to the Special Issue Oxidative Stress in Various Forms and Efficient Antioxidant Pathways in Prokaryotic and Eukaryotic Cells)

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13 pages, 1576 KiB

Open AccessArticle

Increased Adhesiveness of Blood Cells Induced by Mercury Chloride: Protective Effect of Hydroxytyrosol

by Pasquale Perrone, Raquel Ortega-Luna, Caterina Manna, Ángeles Álvarez-Ribelles and Victor Collado-Diaz

Antioxidants 2024, 13(12), 1576; https://doi.org/10.3390/antiox13121576 - 20 Dec 2024

Abstract

Mercury (Hg) is a highly toxic environmental contaminant that can harm human health, ultimately leading to endothelial dysfunction. Hg toxicity is partially mediated by the exposure of the cell membrane’s surface of erythrocytes (RBCs) to phosphatidylserine (PS). In the context of these challenges, [...] Read more.

Mercury (Hg) is a highly toxic environmental contaminant that can harm human health, ultimately leading to endothelial dysfunction. Hg toxicity is partially mediated by the exposure of the cell membrane’s surface of erythrocytes (RBCs) to phosphatidylserine (PS). In the context of these challenges, hydroxytyrosol, a phenolic compound of olive oil, has the ability to mitigate the toxic effects of Hg. This study aims to analyze the effect of Hg on the adhesion of RBCs and polymorphonuclear cells (PMNs) to the vascular endothelium and the potential protective effect of hydroxytyrosol, as these interactions are crucial in the development of cardiovascular diseases (CVDs). RBCs, PMNs, and human vein endothelial cells (HUVECs) were treated with increasing concentrations of HgCl₂ and, in some cases, with hydroxytyrosol, and their adhesion to HUVECs and the expression of adhesion molecules were subsequently analyzed. Our results demonstrate that HgCl₂ significantly increases the adhesion of both RBCs (2.72 ± 0.48 S.E.M., p-value < 0.02) and PMNs (11.19 ± 1.96 S.E.M., p-value < 0.05) to HUVECs and that their adhesiveness is significantly reduced following treatment with hydroxytyrosol (RBCs, 1.2 ± 1.18 S.E.M., p-value < 0.02 and PMNs, 4.04 ± 1.35 S.E.M., p-value < 0.06). Interestingly, HgCl₂ does not alter the expression of adhesion molecules on either HUVECs or RBCs, suggesting that reduced exposure to PS is a key factor in hydroxytyrosol protection against HgCl₂-induced RBC adhesion to the endothelium. On the other hand, HgCl₂ induces increased expression of several PMN adhesion molecules (CD11b 215.4 ± 30.83 S.E.M. p-value < 0.01), while hydroxytyrosol inhibits their expression (e.g., CD11b 149 ± 14.35 S.E.M., p-value < 0.03), which would seem to be the mechanism by which hydroxytyrosol restricts PMN–endothelium interactions. These results provide new insights into the molecular mechanisms through which hydroxytyrosol mitigates the harmful effects of Hg on cardiovascular health, highlighting its potential as a therapeutic agent that can reduce the cardiovascular risk related to heavy metal exposure. Full article

(This article belongs to the Special Issue Oxidative Stress in Hemoglobin and Red Blood Cells)

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24 pages, 8118 KiB

Open AccessArticle

Transcriptomic Characterization Reveals Mitochondrial Involvement in Nrf2/Keap1-Mediated Osteoclastogenesis

by Eiko Sakai and Takayuki Tsukuba

Antioxidants 2024, 13(12), 1575; https://doi.org/10.3390/antiox13121575 - 20 Dec 2024

Abstract

Although osteoclasts play crucial roles in the skeletal system, the mechanisms that underlie oxidative stress during osteoclastogenesis remain unclear. The transcription factor Nrf2 and its suppressor, Keap1, function as central mediators of oxidative stress. To further elucidate the function of Nrf2/Keap1-mediated oxidative stress [...] Read more.

Although osteoclasts play crucial roles in the skeletal system, the mechanisms that underlie oxidative stress during osteoclastogenesis remain unclear. The transcription factor Nrf2 and its suppressor, Keap1, function as central mediators of oxidative stress. To further elucidate the function of Nrf2/Keap1-mediated oxidative stress regulation in osteoclastogenesis, DNA microarray analysis was conducted in this study using wild-type (WT), Keap1 knockout (Keap1 KO), and Nrf2 knockout (Nrf2 KO) osteoclasts. Principal component analysis showed that 403 genes, including Nqo1, Il1f9, and Mmp12, were upregulated in Keap1 KO compared with WT osteoclasts, whereas 24 genes, including Snhg6, Ccdc109b, and Wfdc17, were upregulated in Nrf2 KO compared with WT osteoclasts. Moreover, 683 genes, including Car2, Calcr, and Pate4, were upregulated in Nrf2 KO cells compared to Keap1 KO cells. Functional analysis by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed upregulated genes in Nrf2 KO osteoclasts were mostly enriched in oxidative phosphorylation. Furthermore, GeneMANIA predicted the protein–protein interaction network of novel molecules such as Rufy4 from genes upregulated in Nrf2 KO osteoclasts. Understanding the complex interactions between these molecules may pave the way for developing promising therapeutic strategies against bone metabolic diseases caused by increased osteoclast differentiation under oxidative stress. Full article

(This article belongs to the Special Issue Role of Nrf2 and ROS in Bone Metabolism)

12 pages, 1833 KiB

Open AccessArticle

Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model

by You-Lin Tain, Chien-Ning Hsu, Chih-Yao Hou and Chih-Kuang Chen

Antioxidants 2024, 13(12), 1574; https://doi.org/10.3390/antiox13121574 - 20 Dec 2024

Abstract

Sodium thiosulfate (STS), a precursor of hydrogen sulfide (H₂S), has demonstrated antihypertensive properties. Previous studies have suggested that H₂S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the clinical application of STS is limited by its [...] Read more.

Sodium thiosulfate (STS), a precursor of hydrogen sulfide (H₂S), has demonstrated antihypertensive properties. Previous studies have suggested that H₂S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the clinical application of STS is limited by its rapid release and intravenous administration. To address this, we developed a poly-lactic acid (PLA)-based nanoparticle system for sustained STS delivery and investigated whether weekly treatment with STS-loaded nanoparticles (NPs) could protect against hypertension in a juvenile CKD rat model. Male Sprague Dawley rats, aged three weeks, were fed a diet containing 0.5% adenine for three weeks to induce a model of pediatric CKD. STS-loaded NPs (25 mg/kg) were administered intravenously during weeks 6, 7, and 8, and at week 9, all rats were sacrificed. Treatment with STS-loaded NPs reduced systolic and diastolic blood pressure by 10 mm Hg and 8 mm Hg, respectively, in juvenile CKD rats. The protective effect of STS-loaded NPs was linked to increased renal expression of H₂S-producing enzymes, including cystathionine γ-lyase (CSE) and D-amino acid oxidase (DAO). Additionally, STS-loaded NP therapy restored nitric oxide (NO) signaling, increasing L-arginine levels, which were disrupted in CKD. Furthermore, the beneficial effects of STS-loaded NPs were associated with inhibition of the renin–angiotensin system (RAS) and the enhancement of the NO signaling pathway. Our findings suggest that STS-loaded NP treatment provides sustained STS delivery and effectively reduces hypertension in a juvenile CKD rat model, bringing us closer to the clinical translation of STS-based therapy for pediatric CKD-induced hypertension. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) and Hydrogen Sulfide (H₂S) in Biology, Illness, and Therapies—2nd Edition)

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21 pages, 4656 KiB

Open AccessArticle

Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma

by Hana Mohd and Bozena Michniak-Kohn

Antioxidants 2024, 13(12), 1573; https://doi.org/10.3390/antiox13121573 - 20 Dec 2024

Abstract

Combining anti-cancer agents in cancer therapies is becoming increasingly common because of their improved efficacy, reduced toxicity, and decreased risk of resistance development. Melanoma, a highly aggressive form of skin cancer characterized by limited treatment options due to chemoresistance, poses a considerable challenge [...] Read more.

Combining anti-cancer agents in cancer therapies is becoming increasingly common because of their improved efficacy, reduced toxicity, and decreased risk of resistance development. Melanoma, a highly aggressive form of skin cancer characterized by limited treatment options due to chemoresistance, poses a considerable challenge for effective management. Here, we test the hypothesis that dietary supplements such as thymoquinone (TQ) and curcumin (CU) cooperatively modulate cancer-associated cellular mechanisms to inhibit melanoma progression. Through a series of in vitro experiments utilizing the A375 melanoma cell line, including assessments of cell viability, apoptosis, multicellular tumor spheroid models, reactive oxygen species (ROS) quantification, metabolomics analysis, and RNA sequencing, we established that the combined application of TQ and CU exhibited superior anti-tumor effects compared to their individual use. Our results indicate that the combination treatment significantly inhibited cell viability and induced apoptosis more effectively than either agent alone, with optimal synergy observed at concentrations of 25 µM CU and 10 µM TQ against A375 cells. Additionally, the combination treatment markedly elevated ROS levels, selectively activating the mitochondrial apoptotic pathway via caspase-9. Differential gene expression analysis further revealed a unique synergistic effect of the combination treatment, with enhanced regulation of genes related to oxidative stress and apoptosis. Notably, pathways such as mitochondrial apoptotic signaling and redox homeostasis were more effectively influenced by the combination, with genes such as GPX3, CYP4F11, and HSPB8 cooperatively regulated. Overall, the findings suggest that, in combination, TQ and CU acts synergistically against melanoma; however, further experimental and clinical studies are required to confirm its therapeutic potential. Full article

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21 pages, 4339 KiB

Open AccessArticle

A Combined Extract from Dioscorea bulbifera and Zingiber officinale Mitigates PM_2.5-Induced Respiratory Damage by NF-κB/TGF-β1 Pathway

by In Young Kim, Hyo Lim Lee, Hye Ji Choi, Yeong Hyeon Ju, Yu Mi Heo, Hwa Rang Na, Dong Yeol Lee, Won Min Jeong and Ho Jin Heo

Antioxidants 2024, 13(12), 1572; https://doi.org/10.3390/antiox13121572 - 20 Dec 2024

Abstract

This research evaluated the protective role of a combined extract of Dioscorea bulbifera and Zingiber officinale (DBZO) against respiratory dysfunction caused by particulate matter (PM_2.5) exposure in BALB/c mice. The bioactive compounds identified in the DBZO are catechin, astragalin, 6-gingerol, 8-gingerol, [...] Read more.

This research evaluated the protective role of a combined extract of Dioscorea bulbifera and Zingiber officinale (DBZO) against respiratory dysfunction caused by particulate matter (PM_2.5) exposure in BALB/c mice. The bioactive compounds identified in the DBZO are catechin, astragalin, 6-gingerol, 8-gingerol, and 6-shogaol. DBZO ameliorated cell viability and reactive oxygen species (ROS) production in PM_2.5-stimulated A549 and RPMI 2650 cells. In addition, it significantly alleviated respiratory dysfunction in BALB/c mice exposed to PM_2.5. DBZO improved the antioxidant systems in lung tissues by modulating malondialdehyde (MDA) content, as well as levels of reduced glutathione (GSH) and superoxide dismutase (SOD). Likewise, DBZO restored mitochondrial dysfunction by improving ROS levels, mitochondrial membrane potential, and ATP production. Moreover, DBZO modulated the levels of neutrophils, eosinophils, monocytes, and lymphocytes (specifically CD4⁺, CD8⁺, and CD4⁺IL-4⁺ T cells) in blood and IgE levels in serum. DBZO was shown to regulate the c-Jun N-terminal kinase (JNK) pathway, nuclear factor kappa B (NF-κB) pathway, and transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) pathway. Histopathological observation indicated that DBZO mitigates the increase in alveolar septal thickness. These findings indicate that DBZO is a promising natural agent for improving respiratory health. Full article

(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution, 2nd Edition)

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21 pages, 6323 KiB

Open AccessReview

Mechanisms of Vitamins Inhibiting Ferroptosis

by Meng Zhang, Xin Chen and Yumei Zhang

Antioxidants 2024, 13(12), 1571; https://doi.org/10.3390/antiox13121571 - 20 Dec 2024

Abstract

Ferroptosis is an iron-dependent form of cell death, which is characterized by the uncontrolled and overwhelming peroxidation of cell membrane lipids. Ferroptosis has been implicated in the progression of various pathologies, including steatotic liver, heart failure, neurodegenerative diseases, and diabetes. Targeted inhibition of [...] Read more.

Ferroptosis is an iron-dependent form of cell death, which is characterized by the uncontrolled and overwhelming peroxidation of cell membrane lipids. Ferroptosis has been implicated in the progression of various pathologies, including steatotic liver, heart failure, neurodegenerative diseases, and diabetes. Targeted inhibition of ferroptosis provides a promising strategy to treat ferroptosis-related diseases. Multivitamins, including vitamins A, B, C, D, E, and K, have shown a good ability to inhibit ferroptosis. For example, vitamin A significantly upregulated the expression of several key ferroptotic gatekeepers genes through nuclear retinoic acid receptors and retinoic X receptors (RAR/RXR). Vitamin B6 could compensate for the impaired glutathione (GSH) levels and restore Glutathione peroxidase 4 (GPX4) expression in cells, ultimately inhibiting ferroptosis. Vitamin D could up-regulate the expression of several anti-ferroptosis proteins by activating vitamin D receptors. Vitamin E and hydroquinone vitamin K (VKH₂) can directly inhibit the propagation of lipid peroxidation, thereby inhibiting ferroptosis. In this review, we summarize the currently understood mechanisms by which vitamins inhibit ferroptosis to provide reference information for future research on the development of ferroptosis inhibitors. Full article

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

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22 pages, 12235 KiB

Open AccessArticle

The Focal Induction of Reactive Oxygen Species in Rats as a Trigger of Aortic Valve Degeneration

by Jessica Isabel Selig, Yukiharu Sugimura, Shintaro Katahira, Marco Polidori, Laura Alida Jacobi, Olga Medovoj, Sarah Betke, Mareike Barth, Artur Lichtenberg, Payam Akhyari and Jan-Philipp Minol

Antioxidants 2024, 13(12), 1570; https://doi.org/10.3390/antiox13121570 - 20 Dec 2024

Abstract

Background: Degenerative aortic valve disease (DAVD) is a multifactorial process. We developed an animal model to analyze the isolated, local effect of reactive oxygen species (ROS) on its pathophysiology. Methods: We utilized a photodynamic reaction (PDR) as a source of ROS in the [...] Read more.

Background: Degenerative aortic valve disease (DAVD) is a multifactorial process. We developed an animal model to analyze the isolated, local effect of reactive oxygen species (ROS) on its pathophysiology. Methods: We utilized a photodynamic reaction (PDR) as a source of ROS in the aortic valve by aiming a laser at the aortic valve for 60 min after the administration of a photosensitizer 24 h prior. ROS, laser, and sham groups (n = 7 each) for every observation period (t = 0; t = 8 d; t = 84 d; t = 168 d) were established. The amount of ROS generation; morphological changes; inflammatory, immune, and apoptotic reactions; and hemodynamic changes in the aortic valves were assessed using appropriate histological, immunohistological, immunohistochemical, and echocardiographic methods. Results: The ROS group displayed an increased amount of ROS (p < 0.01) and increased inflammatory activation of the endothelium (p < 0.05) at t = 0. In the ROS group, aortic valves were calcified (p < 0.05) and the transvalvular gradient was increased (p < 0.01) at t = 168 d. Conclusion: The small animal model employed here may serve as a platform for analyzing ROS’s isolated role in the DAVD context. Full article

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

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2 pages, 147 KiB

Open AccessCorrection

Correction: Ogawa et al. Micronutrient Antioxidants for Men (Menevit^®) Improve Sperm Function by Reducing Oxidative Stress, Resulting in Improved Assisted Reproductive Technology Outcomes. Antioxidants 2024, 13, 635

by Seiji Ogawa, Kaori Nishizawa, Masumi Shinagawa, Mikiko Katagiri, Hiroyuki Kikuchi, Hideyuki Kobayashi and Hiroaki Yoshida

Antioxidants 2024, 13(12), 1569; https://doi.org/10.3390/antiox13121569 - 20 Dec 2024

Abstract

In the originally published article [...] Full article

15 pages, 2076 KiB

Open AccessArticle

Bioactive Content and Antioxidant Properties of Spray-Dried Microencapsulates of Peumus boldus M. Leaf Extracts

by Valentina Polanco, Débora Cerdá-Bernad, Issis Quispe-Fuentes, Claudia Bernal and Jéssica López

Antioxidants 2024, 13(12), 1568; https://doi.org/10.3390/antiox13121568 - 20 Dec 2024

Abstract

Boldo (Peumus boldus M.), an plant endemic to central and southern Chile, has been recognized as a medicinal herb, especially its leaves that are rich in bioactive compounds with beneficial properties, such as antioxidant, anti-inflammatory, sedative, and antimicrobial properties, among others. This [...] Read more.

Boldo (Peumus boldus M.), an plant endemic to central and southern Chile, has been recognized as a medicinal herb, especially its leaves that are rich in bioactive compounds with beneficial properties, such as antioxidant, anti-inflammatory, sedative, and antimicrobial properties, among others. This research aimed to evaluate solid-liquid extraction using a response surface methodology to obtain phenolic-rich extracts from boldo leaves and to encapsulate them through spray-drying. A Box-Behnken design was applied to optimize extraction process variables (temperature, time, and solid-liquid ratio). Extracts were characterized in terms of their total phenolic content, with the maximum value obtained being 37.78 mg GAE/g using extraction conditions of a temperature of 100 °C, a time of 60 min, and a solid-liquid ratio of 1:100. The developed microcapsules containing the optimal boldo extracts were characterized (moisture, water activity, scanning electron microscopy, zeta potential, FTIR, total phenolic compounds, antioxidant capacity, and phenolic profile by HPLC-DAD), highlighting their high phenolic content (5.38–5.49 mg GAE/g) and antioxidant capacity, as well as their bioactive content in terms of catechin (445 ± 37 mg/100 g), pyrogallol (304 ± 24 mg/100 g), and epigallocatechin (156 ± 12 mg/100 g). Overall, this study revealed an efficient technique by which to isolate and stabilize bioactive compounds from boldo leaves, with the microcapsules being promising candidates as high added-value ingredients. Full article

(This article belongs to the Special Issue Phenolic Antioxidants)

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14 pages, 1097 KiB

Open AccessReview

Vitamins, Coenzyme Q10, and Antioxidant Strategies to Improve Oocyte Quality in Women with Gynecological Cancers: A Comprehensive Review

by Isaic Alexandru, Daciana Nistor, Alexandru Catalin Motofelea, Bianca-Astrid Cadar (Andone), Andreea Crintea, Carmen Tatu, Gheorghe Nicusor Pop and Andrei Nicolae Csep

Antioxidants 2024, 13(12), 1567; https://doi.org/10.3390/antiox13121567 - 19 Dec 2024

Abstract

Background: Gynecological cancers, including ovarian, cervical, and endometrial cancers, significantly affect both survival and reproductive health in women. Cancer treatments such as chemotherapy and radiotherapy can impair ovarian function, reducing oocyte quality and fertility potential. Objective: This review aims to evaluate how vitamins [...] Read more.

Background: Gynecological cancers, including ovarian, cervical, and endometrial cancers, significantly affect both survival and reproductive health in women. Cancer treatments such as chemotherapy and radiotherapy can impair ovarian function, reducing oocyte quality and fertility potential. Objective: This review aims to evaluate how vitamins and antioxidants can enhance fertility and fertility preservation outcomes for women diagnosed with gynecological cancers, particularly in the context of assisted reproductive technologies (ART). Standard treatments for these cancers, including hysterectomy, bilateral salpingo-oophorectomy, radiation, and chemotherapy, often compromise ovarian function and oocyte quality. This review focuses on the potential role of these interventions in improving oocyte quality, thereby supporting successful fertility preservation and ART outcomes. Methods: A comprehensive narrative review of the current literature was conducted, examining the effects of vitamins A, C, D3, E, and Coenzyme Q10 on oocyte quality, particularly in the context of oxidative stress and inflammation induced by cancer and its treatments. Results: The evidence suggests that certain vitamins and antioxidants may mitigate oxidative damage and enhance oocyte quality. Vitamin A supports cumulus–oocyte complex integrity, while vitamins C and E act as potent antioxidants, reducing oxidative stress in ovarian tissues. Vitamin D3 enhances ovarian reserve markers and modulates inflammatory cytokines. Coenzyme Q10 improves mitochondrial function and reduces DNA damage, increasing oocyte viability and fertilization potential. Conclusions: The incorporation of specific vitamins and antioxidants into fertility preservation strategies may enhance oocyte quality in women with gynecological cancers. Although the preliminary findings are promising, further research is needed to determine optimal dosages and establish standardized protocols for clinical use. Full article

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

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21 pages, 2604 KiB

Open AccessArticle

Circulating Glutathione Peroxidase-3 in Elderly—Association with Renal Function, Cardiovascular Mortality, and Impact of Selenium and Coenzyme Q₁₀ Supplementation

by Jan Alexander, Jan Olav Aaseth, Lutz Schomburg, Thilo Samson Chillon, Anders Larsson and Urban Alehagen

Antioxidants 2024, 13(12), 1566; https://doi.org/10.3390/antiox13121566 (registering DOI) - 19 Dec 2024

Abstract

Low-selenium status was associated with impaired renal function, which improved after selenium and coenzyme Q₁₀ supplementation in an RCT. Here, we evaluated serum glutathione peroxidase-3 (GPx3) and its relation to serum selenium, selenoprotein P (SELENOP), renal function, mortality, and the impact of [...] Read more.

Low-selenium status was associated with impaired renal function, which improved after selenium and coenzyme Q₁₀ supplementation in an RCT. Here, we evaluated serum glutathione peroxidase-3 (GPx3) and its relation to serum selenium, selenoprotein P (SELENOP), renal function, mortality, and the impact of supplementation, which are all important, especially in elderly individuals. In total, 383 study participants (197 receiving selenium yeast and coenzyme Q₁₀ and 186 on a placebo) were evaluated. We applied benchmark dose modelling to determine GPx3 saturation, ANCOVA, Kaplan–Meier, and multivariate Cox proportional regression analyses for mortality evaluations. Selenium and GPx3 activity were modestly correlated. In comparison with SELENOP, GPx3 levelled off at a much lower value, 100 vs. 150 µg Se/L. GPx3 was associated with renal function, but not SELENOP. Supplementation increased glomerular function by ≈23% with an increase in GPx3. Being low in GPx3 displayed twice the risks of mortality in both placebos and active treatments. At serum selenium <100 µg/L, GPx3 activity was dependent on both selenium status and renal function. As renal function is reduced in the elderly, GPx3 is not an appropriate marker of selenium status. Low GPx3 was associated with an increased risk of mortality dependent of selenium status and independent of renal function. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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21 pages, 10410 KiB

Open AccessArticle

Glutathione Involvement in Potato Response to French Marigold Volatile Organic Compounds

by Jelena Savić, Đura Nakarada, Sofija Stupar, Ljiljana Tubić, Milica Milutinović, Miloš Mojović and Nina Devrnja

Antioxidants 2024, 13(12), 1565; https://doi.org/10.3390/antiox13121565 - 19 Dec 2024

Abstract

To elucidate the involvement of glutathione in the mitigation of induced oxidative changes and the sequestration of perceived volatiles in cells, we exposed potato plants to French marigold essential oil. The formation of short-lived radicals, the determination of scavenging activity towards ascorbyl and [...] Read more.

To elucidate the involvement of glutathione in the mitigation of induced oxidative changes and the sequestration of perceived volatiles in cells, we exposed potato plants to French marigold essential oil. The formation of short-lived radicals, the determination of scavenging activity towards ascorbyl and DPPH radicals, and the assessment of the potato plants’ overall intra/extracellular reduction status were performed using electron paramagnetic resonance spectroscopy (EPR). The results showed the presence of hydroxyl radicals in potatoes, with significantly reduced accumulation in exposed plants compared to the control group after 8 h. However, the kinetics of EPR signal intensity change for the pyrrolidine spin probe (3CP) in these plants showed very low reducing potential, suggesting that the antioxidant system acts lethargically and/or the probe has been reoxidized. Total glutathione and its reduced/oxidized form ratio, determined spectrophotometrically, showed that the exposed plants initially had lower glutathione levels with diminutive, reduced form compared to the control. Still, after 8 h, both characteristics were similar to those of the control. RT-qPCR analysis revealed that the volatiles altered the expression of glutathione metabolism-involved genes, especially that of glutathione-S-transferase, after 8 h. Glutathione metabolism was affected by volatiles in the initial response of potato plants exposed to French marigold essential oil, and glutathione molecules were involved in the mitigation of induced oxidative burst. Full article

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20 pages, 5471 KiB

Open AccessSystematic Review

Relevant Serum Endoplasmic Reticulum Stress Biomarkers in Type 2 Diabetes and Its Complications: A Systematic Review and Meta-Analysis

by José Rafael Villafan-Bernal, Francisco Barajas-Olmos, Iris Paola Guzmán-Guzmán, Angélica Martínez-Hernández, Cecilia Contreras-Cubas, Humberto García-Ortiz, Monserrat I. Morales-Rivera, Raigam Jafet Martínez-Portilla and Lorena Orozco

Antioxidants 2024, 13(12), 1564; https://doi.org/10.3390/antiox13121564 - 19 Dec 2024

Abstract

Endoplasmic reticulum stress (ERS) is activated in all cells by stressors such as hyperglycemia. However, it remains unclear which specific serum biomarkers of ERS are consistently altered in type 2 diabetes (T2D). We aimed to identify serum ERS biomarkers that are consistently altered [...] Read more.

Endoplasmic reticulum stress (ERS) is activated in all cells by stressors such as hyperglycemia. However, it remains unclear which specific serum biomarkers of ERS are consistently altered in type 2 diabetes (T2D). We aimed to identify serum ERS biomarkers that are consistently altered in T2D and its complications, and their correlation with metabolic and anthropometric variables. We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). The risk of bias was assessed using the Newcastle–Ottawa scale. Random-effects models weighted by the inverse variance were employed to estimate the standardized mean difference and correlations as effect size measures. Indicators of heterogeneity and meta-regressions were evaluated. Of the 1206 identified studies, 22 were finally included, representing 11,953 subjects (2224 with T2D and 9992 non-diabetic controls). Most studies were of high quality. Compared with controls, subjects with T2D had higher circulating levels of heat shock protein 70 (HSP70; SMD: 2.30, 95% CI 1.13–3.46; p < 0.001) and secretagogin (SMD: 0.60, 95%CI 0.19–1.01; p < 0.001). They also had higher serum levels of peroxiredoxin-1, -2, -4, and -6. Secretagogin inversely correlated with HOMA-IR, yet positively correlated with HOMA-B, HbA1c, and FPG. PRX4 negatively correlated with HbA1c and FPG, while HSP70 positively correlated with HbA1c. In conclusion, six ERS biomarkers are consistently elevated in human T2D and correlate with glycemic control, insulin resistance, and β-cell function. Emerging evidence links serum ERS biomarkers to diabetes complications, but further research should evaluate their prognostic implications. Full article

(This article belongs to the Special Issue Exploring Endoplasmic Reticulum Stress in Disease: The Therapeutic Potential of Natural Pro- and Antioxidant Compounds in Redox Modulation)

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38 pages, 2290 KiB

Open AccessReview

Facts, Dogmas, and Unknowns About Mitochondrial Reactive Oxygen Species in Cancer

by Milagros Junco, Clara Ventura, Florencia Ximena Santiago Valtierra and Eduardo Nestor Maldonado

Antioxidants 2024, 13(12), 1563; https://doi.org/10.3390/antiox13121563 - 19 Dec 2024

Abstract

Cancer metabolism is sustained both by enhanced aerobic glycolysis, characteristic of the Warburg phenotype, and oxidative metabolism. Cell survival and proliferation depends on a dynamic equilibrium between mitochondrial function and glycolysis, which is heterogeneous between tumors and even within the same tumor. During [...] Read more.

Cancer metabolism is sustained both by enhanced aerobic glycolysis, characteristic of the Warburg phenotype, and oxidative metabolism. Cell survival and proliferation depends on a dynamic equilibrium between mitochondrial function and glycolysis, which is heterogeneous between tumors and even within the same tumor. During oxidative phosphorylation, electrons from NADH and FADH₂ originated in the tricarboxylic acid cycle flow through complexes of the electron transport chain. Single electron leaks at specific complexes of the electron transport chain generate reactive oxygen species (ROS). ROS are a concentration-dependent double-edged sword that plays multifaceted roles in cancer metabolism. ROS serve either as signaling molecules favoring cellular homeostasis and proliferation or damage DNA, protein and lipids, causing cell death. Several aspects of ROS biology still remain unsolved. Among the unknowns are the actual levels at which ROS become cytotoxic and if toxicity depends on specific ROS species or if it is caused by a cumulative effect of all of them. In this review, we describe mechanisms of mitochondrial ROS production, detoxification, ROS-induced cytotoxicity, and the use of antioxidants in cancer treatment. We also provide updated information about critical questions on the biology of ROS on cancer metabolism and discuss dogmas that lack adequate experimental demonstration. Overall, this review brings a comprehensive perspective of ROS as drivers of cancer progression, inducers of cell death, and the potential use of antioxidants as anticancer therapy. Full article

(This article belongs to the Special Issue Oxidative Metabolism and Mitochondrial Dysfunction in Metabolic Diseases—2nd Edition)

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21 pages, 8208 KiB

Open AccessArticle

Antioxidant, Anti-Inflammatory, and Anticancer Activities of Five Citrus Peel Essential Oils

by Yurong Li, Wenji Li, Zimao Ye, Chen Ji and Zhiqin Zhou

Antioxidants 2024, 13(12), 1562; https://doi.org/10.3390/antiox13121562 - 19 Dec 2024

Abstract

Citrus peel essential oil (CPEO) is favored by people for its aromatic scent, while also possessing numerous bioactive compounds that are advantageous to human health. This study evaluated the antioxidant, anti-inflammatory, and anticancer activities of CPEOs through cell experiments. The results showed that [...] Read more.

Citrus peel essential oil (CPEO) is favored by people for its aromatic scent, while also possessing numerous bioactive compounds that are advantageous to human health. This study evaluated the antioxidant, anti-inflammatory, and anticancer activities of CPEOs through cell experiments. The results showed that CPEOs could increase the activity of the antioxidant enzyme system and nonenzymatic defence system in H₂O₂-treated RAW 264.7 cells by reducing cellular lipid peroxidation. CPEOs also reduced the nitric oxide production induced by lipopolysaccharide treatment in RAW 264.7 cells while decreasing proinflammatory cytokines expression and increasing anti-inflammatory cytokine expression. Wound healing assays, flow cytometry, and quantitative real-time fluorescent quantitative PCR (qRT-PCR) revealed that CPEOs could induce apoptosis in U87 cells through the mitochondrial apoptotic pathway. These findings indicate that CPEOs possess excellent antioxidant, anti-inflammatory, and anticancer activity potential, making them suitable for use in functional antioxidant and anti-inflammatory foods and nutritional health products. Full article

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

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14 pages, 896 KiB

Open AccessReview

The Influence of Berry-Derived Polyphenol Supplementation on Exercise-Induced Oxidative Stress and Cardiovascular Health in Physically Active Individuals

by Joanna Ruszkowska, Wojciech Drygas and Magdalena Kwaśniewska

Antioxidants 2024, 13(12), 1561; https://doi.org/10.3390/antiox13121561 - 19 Dec 2024

Abstract

Numerous studies have documented that high-intensity or prolonged exercise is associated with increased oxidative stress and modification of antioxidant status. Polyphenol-rich dietary supplements seem to be the compounds that can upregulate the endogenous antioxidant defense system and consequently prevent muscle damage, support recovery. [...] Read more.

Numerous studies have documented that high-intensity or prolonged exercise is associated with increased oxidative stress and modification of antioxidant status. Polyphenol-rich dietary supplements seem to be the compounds that can upregulate the endogenous antioxidant defense system and consequently prevent muscle damage, support recovery. As berry fruits are at the top of the list of the richest polyphenol food sources, supplements containing berries have become the subject of interest in the context of counteracting exercise-induced oxidative stress and the development of cardiovascular diseases. The purpose of this review is to summarize current knowledge on the effects of berry-derived polyphenol supplementation on exercise-induced oxidative stress and cardiovascular health in physically active individuals. Based on the available literature, blackcurrant supplementation, with its richest version being New Zealand blackcurrant extract, is the most commonly explored berry fruit, followed by chokeberries and blueberries. Although several studies have documented the significant and beneficial influence of berry-derived supplements on redox status and cardiovascular response, some inconsistencies remain. The presented findings should be interpreted with caution due the limited number of available studies, particularly with the participation of physically active individuals. Further research is needed to reveal more comprehensive and accurate data concerning the impact of berry-derived supplements on exercise-induced outcomes taking into account the type of supplement, time of administration, and dosage. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Cardiovascular Health, 2nd Edition)

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24 pages, 2034 KiB

Open AccessReview

Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology

by Willibald Wonisch, Franz Tatzber, Meinrad Lindschinger, Andreas Falk, Ulrike Resch, Sabrina Mörkl, Neven Zarkovic and Gerhard Cvirn

Antioxidants 2024, 13(12), 1560; https://doi.org/10.3390/antiox13121560 - 19 Dec 2024

Abstract

One of the most prominent actions of oxidative stress is the attack of free radicals on poylyunsaturated fatty acids (PUFAs), initiating a chain reaction to modify these PUFAs and generate oxidized modifications on all biomolecules. In the last quarter of the 20th century, [...] Read more.

One of the most prominent actions of oxidative stress is the attack of free radicals on poylyunsaturated fatty acids (PUFAs), initiating a chain reaction to modify these PUFAs and generate oxidized modifications on all biomolecules. In the last quarter of the 20th century, intensive research was carried out to identify antibodies against such modifications. In the mid-1990s, the first enzyme-linked immunosorbent assay (ELISA) was introduced to the market, significantly accelerating research activities and knowledge gain. During this pioneering period, the main focus was on cardiovascular diseases, cancer, diabetes, and other diseases associated with oxidative stress. Subsequently, a standard range of these antibodies against oxidized LDL (oLAb) was determined in the population. Furthermore, the impact of exhaustive physical activity and diet on oLAb titers, and the correlation between newborns and mothers after delivery, as well as nutritional intake in newborns, were evaluated. Subsequently, the harmful effects of smoking and many other areas regarding oLAb titer were published, resulting in novel approaches for prognostic and therapeutic options, in particular through studies with antioxidants, which were able to influence oLAb significantly. This review presents an overview of the research activities obtained with this ELISA over the past three decades. Full article

(This article belongs to the Special Issue Development and Validation of Methods for Analysis of Oxidative Stress in Humans and Animals—2nd Edition)

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