Antioxidants

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15 pages, 2555 KiB

Open AccessArticle

Neuroprotective Effect of 4-Phenylbutyric Acid against Photo-Stress in the Retina

by Naymel Alejandra Guzmán Mendoza, Kohei Homma, Hideto Osada, Eriko Toda, Norimitsu Ban, Norihiro Nagai, Kazuno Negishi, Kazuo Tsubota and Yoko Ozawa

Antioxidants 2021, 10(7), 1147; https://doi.org/10.3390/antiox10071147 - 20 Jul 2021

Cited by 9 | Viewed by 2967

Abstract

Exposure to excessive visible light causes retinal degeneration and may influence the progression of retinal blinding diseases. However, there are currently no applied treatments. Here, we focused on endoplasmic reticulum (ER) stress, which can cause cellular degeneration and apoptosis in response to stress. [...] Read more.

Exposure to excessive visible light causes retinal degeneration and may influence the progression of retinal blinding diseases. However, there are currently no applied treatments. Here, we focused on endoplasmic reticulum (ER) stress, which can cause cellular degeneration and apoptosis in response to stress. We analyzed functional, histological, and molecular changes in the light-exposed retina and the effects of administering an ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), in mice. We found that light-induced visual function impairment related to photoreceptor cell loss and outer segment degeneration were substantially suppressed by 4-PBA administration, following attenuated photoreceptor apoptosis. Induction of retinal ER stress soon after light exposure, represented by upregulation of the immunoglobulin heavy chain binding protein (BiP) and C/EBP-Homologous Protein (CHOP), were suppressed by 4-PBA. Concurrently, light-induced oxidative stress markers, Nuclear factor erythroid 2–related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1), and mitochondrial apoptotic markers, B-cell lymphoma 2 apoptosis regulator (Bcl-2)-associated death promoter (Bad), and Bcl-2-associated X protein (Bax), were suppressed by 4-PBA administration. Increased expression of glial fibrillary acidic protein denoted retinal neuroinflammation, and inflammatory cytokines were induced after light exposure; however, 4-PBA acted as an anti-inflammatory. Suppression of ER stress by 4-PBA may be a new therapeutic approach to suppress the progression of retinal neurodegeneration and protect visual function against photo-stress. Full article

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

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14 pages, 3615 KiB

Open AccessArticle

CTLA-2 Alpha Is a Potent Inhibitor of Angiogenesis in Murine Ocular Tissue

by Kazuichi Maruyama, Kazuhito Yoneda, Sunao Sugita, Yoshimi Yamamoto, Masato Koike, Christoph Peters, Yasuo Uchiyama and Kohji Nishida

Antioxidants 2021, 10(3), 456; https://doi.org/10.3390/antiox10030456 - 15 Mar 2021

Cited by 2 | Viewed by 2561

Abstract

Cytotoxic T lymphocyte antigen-2 (CTLA-2) alpha has been reported to suppress the activities of cathepsin L (Cath L), which is deeply involved in angiogenesis. Therefore, we assessed whether CTLA-2 alpha plays a role in angiogenesis in ocular tissue. To establish models of corneal [...] Read more.

Cytotoxic T lymphocyte antigen-2 (CTLA-2) alpha has been reported to suppress the activities of cathepsin L (Cath L), which is deeply involved in angiogenesis. Therefore, we assessed whether CTLA-2 alpha plays a role in angiogenesis in ocular tissue. To establish models of corneal inflammation and experimental choroidal neovascularization (CNV), male C57BL/6J mice (n = 5) underwent corneal suture placement or laser-induced CNV, respectively. Mice were then injected with recombinant CTLA-2 alpha (1 µg) into the peritoneal cavity at day 0 and every 2 days after operation. In vitro experiments were performed to assess the inflammatory response by measuring TNF-alpha secretion in peritoneal cavity exudate cells (PECs) or the proliferation of mouse vascular endothelial cells (mVECs). CTLA-2 alpha treatment dramatically suppressed corneal angiogenesis, as well as laser-induced CNV. Moreover, CTLA-2 alpha inhibited the proliferation of mVECs in vitro, while CTLA-2 alpha abolishment was able to rescue proliferation. However, CTLA-2 alpha could not suppress cytokine secretion from inflammatory cells such as PECs. In summary, CTLA-2 alpha was able to suppress angiogenesis by suppressing endothelial cell proliferation. Further studies are needed to investigate its usefulness as a new antiangiogenic treatment for a variety of conditions, including age-related macular degeneration. Full article

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

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13 pages, 5998 KiB

Open AccessArticle

Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas

by Kyung Woo Kim, Sentaro Kusuhara, Atsuko Katsuyama-Yoshikawa, Sho Nobuyoshi, Megumi Kitamura, Sotaro Mori, Noriyuki Sotani, Kaori Ueda, Wataru Matsumiya, Akiko Miki, Takuji Kurimoto, Hisanori Imai and Makoto Nakamura

Antioxidants 2021, 10(3), 455; https://doi.org/10.3390/antiox10030455 - 15 Mar 2021

Cited by 1 | Viewed by 2067

Abstract

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological [...] Read more.

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8–12 weeks (young) or 45–55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency. Full article

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

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21 pages, 4377 KiB

Open AccessArticle

Intestinal Alkaline Phosphatase Combined with Voluntary Physical Activity Alleviates Experimental Colitis in Obese Mice. Involvement of Oxidative Stress, Myokines, Adipokines and Proinflammatory Biomarkers

by Aleksandra Danielak, Dagmara Wojcik, Agnieszka Mazur-Bialy, Marcin Surmiak, Jan Bilski, Aneta Targosz, Marcin Magierowski, Anna Chmura, Malgorzata Strzalka, Gracjana Krzysiek-Maczka, Katarzyna Magierowska, Urszula Szczyrk, Sławomir Kwiecien, Agata Ptak-Belowska and Tomasz Brzozowski

Antioxidants 2021, 10(2), 240; https://doi.org/10.3390/antiox10020240 - 04 Feb 2021

Cited by 9 | Viewed by 2988

Abstract

Intestinal alkaline phosphatase (IAP) is an essential mucosal defense factor involved in the process of maintenance of gut homeostasis. We determined the effect of moderate exercise (voluntary wheel running) with or without treatment with IAP on the course of experimental murine 2,4,6-trinitrobenzenesulfonic acid [...] Read more.

Intestinal alkaline phosphatase (IAP) is an essential mucosal defense factor involved in the process of maintenance of gut homeostasis. We determined the effect of moderate exercise (voluntary wheel running) with or without treatment with IAP on the course of experimental murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis by assessing disease activity index (DAI), colonic blood flow (CBF), plasma myokine irisin levels and the colonic and adipose tissue expression of proinflammatory cytokines, markers of oxidative stress (SOD2, GPx) and adipokines in mice fed a standard diet (SD) or high-fat diet (HFD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant decrease in CBF, and a significant increase in the colonic expression of tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β and leptin mRNAs and decrease in the mRNA expression of adiponectin. These effects were aggravated in sedentary HFD mice but reduced in exercising animals, potentiated by concomitant treatment with IAP, especially in obese mice. Exercising HFD mice demonstrated a substantial increase in the mRNA for adiponectin and a decrease in mRNA leptin expression in intestinal mucosa and mesenteric fat as compared to sedentary animals. The expression of SOD2 and GPx mRNAs was significantly decreased in adipose tissue in HFD mice, but these effects were reversed in exercising mice with IAP administration. Our study shows for the first time that the combination of voluntary exercise and oral IAP treatment synergistically favored healing of intestinal inflammation, strengthened the antioxidant defense and ameliorated the course of experimental colitis; thus, IAP may represent a novel adjuvant therapy to alleviate inflammatory bowel disease (IBD) in humans. Full article

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

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14 pages, 310 KiB

Open AccessArticle

CARD8 and IL1B Polymorphisms Influence MRI Brain Patterns in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

by Katarina Esih, Katja Goričar, Zvonka Rener-Primec, Vita Dolžan and Aneta Soltirovska-Šalamon

Antioxidants 2021, 10(1), 96; https://doi.org/10.3390/antiox10010096 - 12 Jan 2021

Cited by 7 | Viewed by 2402

Abstract

Inflammation and oxidative stress are recognized as important contributors of brain injury in newborns due to a perinatal hypoxic-ischemic (HI) insult. Genetic variability in these pathways could influence the response to HI and the outcome of brain injury. The aim of our study [...] Read more.

Inflammation and oxidative stress are recognized as important contributors of brain injury in newborns due to a perinatal hypoxic-ischemic (HI) insult. Genetic variability in these pathways could influence the response to HI and the outcome of brain injury. The aim of our study was to evaluate the impact of common single-nucleotide polymorphisms in the genes involved in inflammation and response to oxidative stress on brain injury in newborns after perinatal HI insult based on the severity and pattern of magnetic resonance imaging (MRI) findings. The DNA of 44 subjects was isolated from buccal swabs. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1B rs16944, IL1B rs1143623, IL1B rs1071676, TNF rs1800629, CAT rs1001179, SOD2 rs4880, and GPX1 rs1050450. Polymorphism in CARD8 was found to be protective against HI brain injury detected by MRI overall findings. Polymorphisms in IL1B were associated with posterior limb of internal capsule, basal ganglia, and white matter brain patterns determined by MRI. Our results suggest a possible association between genetic variability in inflammation- and antioxidant-related pathways and the severity of brain injury after HI insult in newborns. Full article

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

13 pages, 2332 KiB

Open AccessArticle

The Time-Course of Antioxidant Irisin Activity: Role of the Nrf2/HO-1/HMGB1 Axis

by Agnieszka Irena Mazur-Bialy and Ewa Pocheć

Antioxidants 2021, 10(1), 88; https://doi.org/10.3390/antiox10010088 - 11 Jan 2021

Cited by 26 | Viewed by 3576

Abstract

The production of free radicals is one of the basic mechanisms giving rise to the antimicrobial activity of macrophages; however, excessive accumulation of reactive oxygen species (ROS) can lead to cell damage, cell death, and release of the highly proinflammatory alarmin high-mobility group [...] Read more.

The production of free radicals is one of the basic mechanisms giving rise to the antimicrobial activity of macrophages; however, excessive accumulation of reactive oxygen species (ROS) can lead to cell damage, cell death, and release of the highly proinflammatory alarmin high-mobility group box 1 (HMGB1). This study aimed to evaluate the kinetics of antioxidant properties of the adipomyokine irisin administered shortly before or after macrophage activation to assess its effect on the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/HMGB1 pathway. The studies were performed on RAW 264.7 mouse macrophages treated with irisin (0, 25, and 50 nM) 2 h before or after lipopolysaccharide (LPS) stimulation. The effectiveness of respiratory burst and the expression of key factors of the antioxidant pathway, such as HO-1, Nrf2, superoxide dismutase 1 (SOD-1), SOD-2, glutathione peroxidase (GPx), catalase-9 (Cat-9), and HMGB1, were assessed. Irisin (50 nM) effectively reduced the free-radical production by macrophages. Furthermore, in both models, irisin altered the kinetics of expression of key factors of the downstream Nrf2/HO-1/HMGB1 pathway, leading to the increased production of Nrf2 and HO-1 and significantly reduced expression and release of HMGB1. In conclusion, irisin is a modulator of the Nrf2/HO-1/HMGB1 pathway and shows antioxidative and anti-inflammatory effects when administered both before and shortly after the activation of inflammatory mechanisms in mouse macrophages. Full article

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

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15 pages, 1638 KiB

Open AccessArticle

Rapid Liquid Chromatography—Tandem Mass Spectrometry Analysis of Two Urinary Oxidative Stress Biomarkers: 8-oxodG and 8-isoprostane

by Nicolas Sambiagio, Jean-Jacques Sauvain, Aurélie Berthet, Reto Auer, Anna Schoeni and Nancy B. Hopf

Antioxidants 2021, 10(1), 38; https://doi.org/10.3390/antiox10010038 - 31 Dec 2020

Cited by 6 | Viewed by 2630

Abstract

Human biomonitoring of oxidative stress relies on urinary effect biomarkers such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and 8-iso-prostaglandin F2α (8-isoprostane); however, their levels reported for similar populations are inconsistent in the scientific literature. One of the reasons is the multitude of analytical methods with varying [...] Read more.

Human biomonitoring of oxidative stress relies on urinary effect biomarkers such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and 8-iso-prostaglandin F2α (8-isoprostane); however, their levels reported for similar populations are inconsistent in the scientific literature. One of the reasons is the multitude of analytical methods with varying degrees of selectivity used to quantify these biomarkers. Single-analyte methods are often used, requiring multiple injections that increase both time and cost. We developed a rapid ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to quantify both urinary biomarkers simultaneously. A reversed-phase column using a gradient consisting of 0.1% acetic acid in water and 0.1% acetic acid in methanol/acetonitrile (70:30) was used for separation. The MS detection was by positive (8-oxodG) and negative (8-isoprostane) ion-mode by multiple reaction monitoring. Very low limit of detection (<20 pg/mL), excellent linearity (R2 > 0.999), accuracy (near 100%), and precision (CV < 10%) both for intra-day and inter-day experiments were achieved, as well as high recovery rates (>91%). Matrix effects were observed but were compensated by using internal standards. Our newly developed method is applicable for biomonitoring studies as well as large epidemiological studies investigating the effect of oxidative damage, as it requires only minimal clean up using solid phase extraction. Full article

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

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11 pages, 281 KiB

Open AccessArticle

Whole-Body Cryostimulation Improves Inflammatory Endothelium Parameters and Decreases Oxidative Stress in Healthy Subjects

by Agata Stanek, Tomasz Wielkoszyński, Stanisław Bartuś and Armand Cholewka

Antioxidants 2020, 9(12), 1308; https://doi.org/10.3390/antiox9121308 - 21 Dec 2020

Cited by 15 | Viewed by 2242

Abstract

Background: The purpose of this study was to estimate the effect of whole-body cryostimulation (WBC) and subsequent kinesiotherapy on inflammatory endothelium and oxidative stress parameters in healthy subjects. Methods: The effects of ten WBC procedures lasting 3 min per day and followed by [...] Read more.

Background: The purpose of this study was to estimate the effect of whole-body cryostimulation (WBC) and subsequent kinesiotherapy on inflammatory endothelium and oxidative stress parameters in healthy subjects. Methods: The effects of ten WBC procedures lasting 3 min per day and followed by a 60-min session of kinesiotherapy on oxidative stress and inflammatory endothelium parameters in healthy subjects (WBC group n = 32) were analyzed. The WBC group was compared to a kinesiotherapy only (KT; n = 16) group. The following parameters were estimated one day before the start, and one day after the completion of the studies: oxidative stress parameters (the total antioxidant capacity of plasma (FRAP), paraoxonase-1 activity (PON-1), and total oxidative status (TOS)) and inflammatory endothelium parameters (myeloperoxidase activity (MPO), serum amyloid A (SAA), and sCD40L levels). Results: A significant decrease of PON-1 and MPO activities and TOS, SAA, and sCD40L levels as well as a significant FRAP increase were observed in the WBC group after the treatment. In addition, the SAA levels and PON-1 activity decreased significantly after the treatment in both groups, but the observed decrease of these parameters in the WBC group was higher in comparison to the KT group. Conclusion: WBC procedures have a beneficial impact on inflammatory endothelium and oxidative stress parameters in healthy subjects, therefore they may be used as a wellness method. Full article

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

11 pages, 250 KiB

Open AccessArticle

Evaluation of Redox Profiles of the Serum and Aqueous Humor in Patients with Primary Open-Angle Glaucoma and Exfoliation Glaucoma

by Yuji Takayanagi, Yasuyuki Takai, Sachiko Kaidzu and Masaki Tanito

Antioxidants 2020, 9(12), 1305; https://doi.org/10.3390/antiox9121305 - 19 Dec 2020

Cited by 14 | Viewed by 1907

Abstract

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous [...] Read more.

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH. Full article

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

23 pages, 4714 KiB

Open AccessArticle

Differential Sex-Dependent Regulation of the Alveolar Macrophage miRNome of SP-A2 and co-ex (SP-A1/SP-A2) and Sex Differences Attenuation after 18 h of Ozone Exposure

by Nithyananda Thorenoor, David S. Phelps and Joanna Floros

Antioxidants 2020, 9(12), 1190; https://doi.org/10.3390/antiox9121190 - 27 Nov 2020

Cited by 6 | Viewed by 2440

Abstract

Background: Human SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, and their genetic variants differentially impact alveolar macrophage (AM) functions and regulation, including the miRNome. We investigated whether miRNome differences previously observed between AM from SP-A2 and SP-A1/SP-A2 mice are due to [...] Read more.

Background: Human SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, and their genetic variants differentially impact alveolar macrophage (AM) functions and regulation, including the miRNome. We investigated whether miRNome differences previously observed between AM from SP-A2 and SP-A1/SP-A2 mice are due to continued qualitative differences or a delayed response of mice carrying a single gene. Methods: Human transgenic (hTG) mice, carrying SP-A2 or both SP-A genes, and SP-A-KO mice were exposed to filtered air (FA) or ozone (O₃)_. AM miRNA levels, target gene expression, and pathways determined 18 h after O₃ exposure. RESULTS: We found (a) differences in miRNome due to sex, SP-A genotype, and exposure; (b) miRNome of both sexes was largely downregulated by O₃, and co-ex had fewer changed (≥2-fold) miRNAs than either group; (c) the number and direction of the expression of genes with significant changes in males and females in co-ex are almost the opposite of those in SP-A2; (d) the same pathways were found in the studied groups; and (e) O₃ exposure attenuated sex differences with a higher number of genotype-dependent and genotype-independent miRNAs common in both sexes after O₃ exposure. Conclusion: Qualitative differences between SP-A2 and co-ex persist 18 h post-O₃, and O₃ attenuates sex differences. Full article

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

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12 pages, 233 KiB

Open AccessArticle

Evaluation of Relevance between Advanced Glycation End Products and Diabetic Retinopathy Stages Using Skin Autofluorescence

by Yuji Takayanagi, Mikihiro Yamanaka, Jo Fujihara, Yotaro Matsuoka, Yuko Gohto, Akira Obana and Masaki Tanito

Antioxidants 2020, 9(11), 1100; https://doi.org/10.3390/antiox9111100 - 09 Nov 2020

Cited by 18 | Viewed by 2351

Abstract

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A [...] Read more.

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR. Full article

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

14 pages, 2773 KiB

Open AccessArticle

BMS-986020, a Specific LPA₁ Antagonist, Provides Neuroprotection against Ischemic Stroke in Mice

by Bhakta Prasad Gaire, Arjun Sapkota and Ji Woong Choi

Antioxidants 2020, 9(11), 1097; https://doi.org/10.3390/antiox9111097 - 08 Nov 2020

Cited by 11 | Viewed by 3547

Abstract

Stroke is a leading cause of death. Stroke survivors often suffer from long-term functional disability. This study demonstrated neuroprotective effects of BMS-986020 (BMS), a selective lysophosphatidic acid receptor 1 (LPA₁) antagonist under clinical trials for lung fibrosis and psoriasis, against both [...] Read more.

Stroke is a leading cause of death. Stroke survivors often suffer from long-term functional disability. This study demonstrated neuroprotective effects of BMS-986020 (BMS), a selective lysophosphatidic acid receptor 1 (LPA₁) antagonist under clinical trials for lung fibrosis and psoriasis, against both acute and sub-acute injuries after ischemic stroke by employing a mouse model with transient middle cerebral artery occlusion (tMCAO). BMS administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, neurological deficits, and cell apoptosis at day 1 after tMCAO. Neuroprotective effects of BMS were preserved even when administered at 3 h after reperfusion. Neuroprotection by BMS against acute injuries was associated with attenuation of microglial activation and lipid peroxidation in post-ischemic brains. Notably, repeated BMS administration daily for 14 days after tMCAO exerted long-term neuroprotection in tMCAO-challenged mice, as evidenced by significantly attenuated neurological deficits and improved survival rate. It also attenuated brain tissue loss and cell apoptosis in post-ischemic brains. Mechanistically, it significantly enhanced neurogenesis and angiogenesis in injured brains. A single administration of BMS provided similar long-term neuroprotection except survival rate. Collectively, BMS provided neuroprotection against both acute and sub-acute injuries of ischemic stroke, indicating that BMS might be an appealing therapeutic agent to treat ischemic stroke. Full article

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

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13 pages, 3304 KiB

Open AccessArticle

Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

by Hyun Hwangbo, Min Yeong Kim, Seon Yeong Ji, So Young Kim, Hyesook Lee, Gi-Young Kim, Cheol Park, Young-Sam Keum, Su Hyun Hong, Jaehun Cheong and Yung Hyun Choi

Antioxidants 2020, 9(11), 1040; https://doi.org/10.3390/antiox9111040 - 23 Oct 2020

Cited by 29 | Viewed by 4015

Abstract

Non-alcoholic fatty liver disease (NAFLD) causes liver dysfunction and is associated with obesity and type 2 diabetes. Chronic inflammation is associated not only with the development of NAFLD, but also with hepatic diseases, including steatohepatitis, cirrhosis, and hepatocellular carcinoma. Auranofin is a treatment [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) causes liver dysfunction and is associated with obesity and type 2 diabetes. Chronic inflammation is associated not only with the development of NAFLD, but also with hepatic diseases, including steatohepatitis, cirrhosis, and hepatocellular carcinoma. Auranofin is a treatment for rheumatoid arthritis and has recently been reported to have potential effects against a variety of diseases, including inflammation, cancer, and viral infection. In this study, auranofin may be considered as a new treatment for the management of metabolic syndrome, as well as in the treatment of NAFLD through immunomodulation. To determine the effect of auranofin on NAFLD, C57BL/6 mice were randomly grouped, fed a regular diet or a high fat diet (HFD), and injected with normal saline or auranofin for 8 weeks. Auranofin significantly decreased the body weight, epididymal fat weight, serum aspartate aminotransferase (AST), and glucose, as well as the serum triglyceride, cholesterol, and low-density lipoprotein cholesterol levels as compared to the HFD group. We also observed that hepatic steatosis was increased in the HFD group and was suppressed by auranofin treatment. In addition, auranofin suppressed the expressions of interleukin (IL)-1β, IL-18, caspase-1, and the NOD-like receptor family pyrin domain containing 3 (NLRP3) in the liver tissue. Furthermore, the expression of NADPH oxidase 4 and peroxisome proliferator-activated receptor γ (PPARγ), which are a major source of oxidative stress and a regulator of adipogenesis, respectively, were also decreased by auranofin. In addition, primary mouse hepatocytes were incubated with lipopolysaccharide (LPS) and palmitic acid (PA) to induce lipid accumulation and hepatic inflammation for an in vitro model. Auranofin could significantly inhibit LPS- and PA-induced inflammatory activity including nitric oxide and NLRP3 inflammasome-mediated cytokines. The results of this study demonstrate that auranofin treatment inhibits the characteristics of NAFLD through the inhibition of NLRP3 inflammasome. Therefore, auranofin may have potential as a candidate for improving NAFLD symptoms. Full article

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

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15 pages, 1052 KiB

Open AccessArticle

Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

by Fatou Gueye Tall, Cyril Martin, El hadji Malick Ndour, Camille Faes, Indou Déme Ly, Vincent Pialoux, Philippe Connes, Papa Madieye Gueye, Rokhaya Ndiaye Diallo, Céline Renoux, Ibrahima Diagne, Pape Amadou Diop, Aynina Cissé, Philomène Lopez Sall and Philippe Joly

Antioxidants 2020, 9(9), 863; https://doi.org/10.3390/antiox9090863 - 14 Sep 2020

Cited by 4 | Viewed by 2585

Abstract

Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs2333227) on [...] Read more.

Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs2333227) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity. Full article

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

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15 pages, 1986 KiB

Open AccessArticle

Anti-Inflammatory Activity of Kurarinone Involves Induction of HO-1 via the KEAP1/Nrf2 Pathway

by Sakiko Nishikawa, Yasumichi Inoue, Yuka Hori, Chiharu Miyajima, Daisuke Morishita, Nobumichi Ohoka, Shigeaki Hida, Toshiaki Makino and Hidetoshi Hayashi

Antioxidants 2020, 9(9), 842; https://doi.org/10.3390/antiox9090842 - 09 Sep 2020

Cited by 28 | Viewed by 5935

Abstract

Kurarinone, a flavonoid isolated from the roots of Sophora flavescens, was suggested to exert potent antioxidant and immunosuppressive effects. However, the underlying mechanisms remain unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates the antioxidant defense [...] Read more.

Kurarinone, a flavonoid isolated from the roots of Sophora flavescens, was suggested to exert potent antioxidant and immunosuppressive effects. However, the underlying mechanisms remain unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates the antioxidant defense system with anti-inflammatory activity. In the present study, we demonstrated that kurarinone activated Nrf2 and increased the expression of antioxidant enzymes, including heme oxygenase-1 (HO-1). Mechanistically, kurarinone downregulated the expression of kelch-like ECH-associated protein 1 (KEAP1), subsequently leading to the activation of Nrf2. Kurarinone also inhibited the expression of the inflammatory cytokine, interleukin (IL)-1β, and inducible nitric oxide synthase (iNos) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The overexpression of HO-1 suppressed the LPS-induced production of inflammatory mediators in RAW264.7 cells, and the immunosuppressive effects of kurarinone were partially inhibited by a treatment with Tin Protomorphyrin IX (TinPPIX), an inhibitor of HO-1. These results indicate that kurarinone activates the KEAP1/Nrf2 pathway to induce HO-1 expression, thereby exerting immunosuppressive effects. Full article

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

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11 pages, 282 KiB

Open AccessFeature PaperArticle

Advanced Glycation End Product Accumulation in Subjects with Open-Angle Glaucoma with and without Exfoliation

by Tomoki Shirakami, Mikihiro Yamanaka, Jo Fujihara, Yotaro Matsuoka, Yuko Gohto, Akira Obana and Masaki Tanito

Antioxidants 2020, 9(8), 755; https://doi.org/10.3390/antiox9080755 - 15 Aug 2020

Cited by 12 | Viewed by 3023

Abstract

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which [...] Read more.

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which is a measurement of AGEs’ accumulation, was compared among Japanese patients with glaucoma (316 with primary open-angle glaucoma (PG) and 127 exfoliation syndrome and glaucoma (EG)) and controls (133 nonglaucomatous controls) (mean age 71.6 ± 12.8 years, 254 men and 322 women). The sAF values were estimated from the middle fingertip using a 365 nm light-emitting diode for excitation and detection at 440 nm emission light. The estimated AGE values (arbitrary unit) were 0.56 ± 0.15, 0.56 ± 0.11, and 0.61 ± 0.11 in the control, PG, and EG groups, respectively (p < 0.0001, analysis of variance); and were significantly higher in the EG group than the control (p = 0.0007) and PG (p < 0.0001) groups. After adjustment for various demographic parameters by multivariate analyses, male sex (standard β = 0.23), EG (0.19), and diabetes (0.09) were associated with higher AGE levels; PG (−0.18) and smoking (−0.19) were associated with lower AGE levels. Age, visual acuity, intraocular pressure, glaucoma medications, lens status, and systemic hypertension were not associated with AGEs. The high AGE level in EG suggested that specific oxidation and glycation mechanisms underlie the glaucoma pathogenesis associated with pseudoexfoliation syndrome. Full article

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

13 pages, 1656 KiB

Open AccessArticle

Is Sleep Associated with the S-Klotho Anti-Aging Protein in Sedentary Middle-Aged Adults? The FIT-AGEING Study

by Sol Mochón-Benguigui, Almudena Carneiro-Barrera, Manuel J. Castillo and Francisco J. Amaro-Gahete

Antioxidants 2020, 9(8), 738; https://doi.org/10.3390/antiox9080738 - 12 Aug 2020

Cited by 6 | Viewed by 3139

Abstract

Sleep and Klotho have both been closely related to the ageing process, both playing a substantial role in the endocrine and immune systems and, thereby, in oxidative stress and chronic inflammation. However, there are no studies elucidating the relationship between sleep and Klotho. [...] Read more.

Sleep and Klotho have both been closely related to the ageing process, both playing a substantial role in the endocrine and immune systems and, thereby, in oxidative stress and chronic inflammation. However, there are no studies elucidating the relationship between sleep and Klotho. Therefore, this study investigated the association of sleep quantity and quality with the shed form of the α-Klotho gene (S-Klotho plasma levels) in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for the present study. Objective sleep quality parameters (total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE)) were determined using a wrist-worn accelerometer over seven consecutive days, and the subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI; higher scores indicate worse sleep quality). The S-Klotho plasma levels were measured in the ethylenediaminetetraacetic acid plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. Objective sleep parameters were associated with the S-Klotho plasma levels only after including the age, fat mass percentage, and lean mass index as covariates. A direct relationship was observed between the subjective sleep quality (inverse of PSQI scores) and the S-Klotho plasma levels in sedentary middle-aged adults. Improving sleep quantity and quality could be considered an anti-aging therapeutic approach for the prevention, slowing, and even reversal of the physiological decline and degenerative pathologies that are certainly related to the aging process. Full article

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

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19 pages, 559 KiB

Open AccessArticle

Antioxidants and Oxidative Stress in Children: Influence of Puberty and Metabolically Unhealthy Status

by Azahara I. Rupérez, María D. Mesa, Augusto Anguita-Ruiz, Esther M. González-Gil, Rocío Vázquez-Cobela, Luis A. Moreno, Ángel Gil, Mercedes Gil-Campos, Rosaura Leis, Gloria Bueno and Concepción M. Aguilera

Antioxidants 2020, 9(7), 618; https://doi.org/10.3390/antiox9070618 - 15 Jul 2020

Cited by 21 | Viewed by 3431

Abstract

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically [...] Read more.

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically healthy (MH) prepubertal and pubertal children and their associations with pro-inflammatory and endothelial damage biomarkers, taking puberty into account. A total of 1444 Spanish children aged 3–17 years (48.9% males, 66% prepubertal, 47.1% with obesity) were recruited. Blood pressure, anthropometric and biochemical parameters were measured, and children were categorized as having a MU or MH status according to risk factors. Retinol, carotenes, tocopherols, total antioxidant capacity (TAC), oxidized low-density lipoprotein and selected pro-inflammatory and endothelial damage biomarkers were analyzed. General linear models adjusted for age, sex, recruitment center and body mass index, partial correlations and stepwise linear regressions were performed. Lower carotenes and tocopherols levels were found in MU than in MH children. Plasma TAC was lower in prepubertal and higher in pubertal children with obesity compared to normal-weight children. Antioxidants and oxidative stress biomarkers showed novel associations with several pro-inflammatory and endothelial damage biomarkers, with pubertal differences, supporting the importance of considering both the antioxidant and oxidative stress status and puberty in the prevention of metabolic diseases in childhood. Full article

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

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13 pages, 281 KiB

Open AccessArticle

Ocular and Systemic Effects of Antioxidative Supplement Use in Young and Healthy Adults: Real-World Cross-Sectional Data

by Sakiko Minami, Norihiro Nagai, Misa Suzuki, Atsuro Uchida, Hajime Shinoda, Kazuo Tsubota and Yoko Ozawa

Antioxidants 2020, 9(6), 487; https://doi.org/10.3390/antiox9060487 - 03 Jun 2020

Viewed by 2397

Abstract

Randomized controlled studies have shown that antioxidative supplements are effective in suppressing the progression of age-related macular degeneration and visual display terminal syndrome. However, effects of their general use in the real-world and by young and healthy individuals have not been well documented. [...] Read more.

Randomized controlled studies have shown that antioxidative supplements are effective in suppressing the progression of age-related macular degeneration and visual display terminal syndrome. However, effects of their general use in the real-world and by young and healthy individuals have not been well documented. We analyzed 27 participants who were under 35 years of age and had no diagnosed diseases. Mean functional visual acuity (FVA) score and visual maintenance ratio, which represent quick recognition of a target, both measured using FVA system, were better (both p < 0.01) in subjects who had had regular antioxidative supplement intake for more than 2 months (11 participants) compared with those who had not. Systemic data, i.e., total cholesterol, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) levels, which correspond to chronic low-grade inflammation, were lower (all p < 0.05) in the former. Overall, hs-CRP levels had a correlation with total cholesterol (p < 0.05) and a trend of correlation with HbA1c (p = 0.054) levels. Thus, current real-world data showed that young, healthy participants who had a regular intake of antioxidative supplements had better visual acuity and systemic levels of metabolic and low-grade inflammation markers. This study will help promote future research into the effects of general antioxidative supplement use. Full article

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

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16 pages, 6349 KiB

Open AccessArticle

Brain Transcriptome Analysis Links Deficiencies of Stress-Responsive Proteins to the Pathomechanism of Kii ALS/PDC

by Satoru Morimoto, Mitsuru Ishikawa, Hirotaka Watanabe, Miho Isoda, Masaki Takao, Shiho Nakamura, Fumiko Ozawa, Yoshifumi Hirokawa, Shigeki Kuzuhara, Hideyuki Okano and Yasumasa Kokubo

Antioxidants 2020, 9(5), 423; https://doi.org/10.3390/antiox9050423 - 14 May 2020

Cited by 7 | Viewed by 3288

Abstract

Amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC) is a unique endemic neurodegenerative disease, with high-incidence foci in Kii Peninsula, Japan. To gather new insights into the pathological mechanisms underlying Kii ALS/PDC, we performed transcriptome analyses of patient brains. We prepared frozen brains from [...] Read more.

Amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC) is a unique endemic neurodegenerative disease, with high-incidence foci in Kii Peninsula, Japan. To gather new insights into the pathological mechanisms underlying Kii ALS/PDC, we performed transcriptome analyses of patient brains. We prepared frozen brains from three individuals without neurodegenerative diseases, three patients with Alzheimer’s disease, and 21 patients with Kii ALS/PDC, and then acquired microarray data from cerebral gray and white matter tissues. Microarray results revealed that expression levels of genes associated with heat shock proteins, DNA binding/damage, and senescence were significantly altered in patients with ALS/PDC compared with healthy individuals. The RNA expression pattern observed for ALS-type brains was similar to that of PDC-type brains. Additionally, pathway and network analyses indicated that the molecular mechanism underlying ALS/PDC may be associated with oxidative phosphorylation of mitochondria, ribosomes, and the synaptic vesicle cycle; in particular, upstream regulators of these mechanisms may be found in synapses and during synaptic trafficking. Furthermore, phenotypic differences between ALS-type and PDC-type were observed, based on HLA haplotypes. In conclusion, determining the relationship between stress-responsive proteins, synaptic dysfunction, and the pathogenesis of ALS/PDC in the Kii peninsula may provide new understanding of this mysterious disease. Full article

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

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Review

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19 pages, 2296 KiB

Open AccessReview

Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry

by Pamela A. Nono Nankam, Télesphore B. Nguelefack, Julia H. Goedecke and Matthias Blüher

Antioxidants 2021, 10(4), 622; https://doi.org/10.3390/antiox10040622 - 19 Apr 2021

Cited by 20 | Viewed by 5065

Abstract

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption [...] Read more.

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities. Full article

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

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28 pages, 858 KiB

Open AccessReview

Nutraceuticals against Oxidative Stress in Autoimmune Disorders

by Carmen Mannucci, Marco Casciaro, Emanuela Elisa Sorbara, Fabrizio Calapai, Eleonora Di Salvo, Giovanni Pioggia, Michele Navarra, Gioacchino Calapai and Sebastiano Gangemi

Antioxidants 2021, 10(2), 261; https://doi.org/10.3390/antiox10020261 - 08 Feb 2021

Cited by 31 | Viewed by 6442

Abstract

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called “phytochemicals”. [...] Read more.

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called “phytochemicals”. Most of these substances are responsible for the positive properties of fruits and vegetables, which are an essential part of a healthy life with roles in ameliorating chronic illnesses and favoring longevity. Nutraceuticals are substances contained in a food or fragment of it influencing health with positive effects on health helping in precenting or treating disorders. We conducted a review illustrating the principal applications of nutraceuticals in autoimmune disorders. Literature reported several studies about exogenous dietary antioxidant supplementation in diverse autoimmune diseases such as rheumatoid arthritis, lupus, diabetes, and multiple sclerosis. In these pathologies, promising results were obtained in some cases. Positive outcomes were generally associated with a reduction of oxidative stress parameters and a boost to antioxidant systems, and sometimes with anti-inflammatory effects. The administration of exogenous substances through food derivates or dietary supplements following scientific standardization was demonstrated to be effective. Further bias-free and extended studies should be conducted that include ever-increasing oxidative stress biomarkers. Full article

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

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26 pages, 2305 KiB

Open AccessReview

The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

by Rosa Vona, Lucia Pallotta, Martina Cappelletti, Carola Severi and Paola Matarrese

Antioxidants 2021, 10(2), 201; https://doi.org/10.3390/antiox10020201 - 30 Jan 2021

Cited by 111 | Viewed by 17345

Abstract

Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its [...] Read more.

Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies Full article

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

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32 pages, 2838 KiB

Open AccessReview

The Potential Benefit of Monitoring Oxidative Stress and Inflammation in the Prevention of Non-Communicable Diseases (NCDs)

by Neda Seyedsadjadi and Ross Grant

Antioxidants 2021, 10(1), 15; https://doi.org/10.3390/antiox10010015 - 27 Dec 2020

Cited by 38 | Viewed by 6431

Abstract

The significant increase in worldwide morbidity and mortality from non-communicable diseases (NCDs) indicates that the efficacy of existing strategies addressing this crisis may need improvement. Early identification of the metabolic irregularities associated with the disease process may be a key to developing early [...] Read more.

The significant increase in worldwide morbidity and mortality from non-communicable diseases (NCDs) indicates that the efficacy of existing strategies addressing this crisis may need improvement. Early identification of the metabolic irregularities associated with the disease process may be a key to developing early intervention strategies. Unhealthy lifestyle behaviours are well established drivers of the development of several NCDs, but the impact of such behaviours on health can vary considerably between individuals. How can it be determined if an individual’s unique set of lifestyle behaviours is producing disease? Accumulating evidence suggests that lifestyle-associated activation of oxidative and inflammatory processes is primary driver of the cell and tissue damage which underpins the development of NCDs. However, the benefit of monitoring subclinical inflammation and oxidative activity has not yet been established. After reviewing relevant studies in this context, we suggest that quantification of oxidative stress and inflammatory biomarkers during the disease-free prodromal stage of NCD development may have clinical relevance as a timely indicator of the presence of subclinical metabolic changes, in the individual, portending the development of disease. Monitoring markers of oxidative and inflammatory activity may therefore enable earlier and more efficient strategies to both prevent NCD development and/or monitor the effectiveness of treatment. Full article

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

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21 pages, 1052 KiB

Open AccessReview

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

by Erika Ramos-Tovar and Pablo Muriel

Antioxidants 2020, 9(12), 1279; https://doi.org/10.3390/antiox9121279 - 15 Dec 2020

Cited by 147 | Viewed by 6423

Abstract

Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form the fibrotic tissue that leads to hepatic fibrosis. Reactive oxygen species (ROS) can directly activate HSCs or induce inflammation or programmed cell death, especially pyroptosis, [...] Read more.

Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form the fibrotic tissue that leads to hepatic fibrosis. Reactive oxygen species (ROS) can directly activate HSCs or induce inflammation or programmed cell death, especially pyroptosis, in hepatocytes, which in turn activates HSCs and fibroblasts to produce ECM proteins. Therefore, antioxidants and the nuclear factor E2-related factor-2 signaling pathway play critical roles in modulating the profibrogenic response. The master proinflammatory factors nuclear factor-κB (NF-κB) and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome may coordinate to produce and activate profibrogenic molecules such as interleukins 1β and 18, which effectively activate HSCs, to produce large amounts of fibrotic proteins. Furthermore, the NLRP3 inflammasome activates pro-caspase 1, which is upregulated by NF-κB, to produce caspase 1, which induces pyroptosis via gasdermin and the activation of HSCs. ROS play central roles in the activation of the NF-κB and NLRP3 signaling pathways via IκB (an inhibitor of NF-κB) and thioredoxin-interacting protein, respectively, thereby linking the molecular mechanisms of oxidative stress, inflammation and fibrosis. Elucidating these molecular pathways may pave the way for the development of therapeutic tools to interfere with specific targets. Full article

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

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28 pages, 908 KiB

Open AccessReview

Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)

by Isabel Hinarejos, Candela Machuca, Paula Sancho and Carmen Espinós

Antioxidants 2020, 9(10), 1020; https://doi.org/10.3390/antiox9101020 - 20 Oct 2020

Cited by 40 | Viewed by 7445

Abstract

The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are [...] Read more.

The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation. Full article

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

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20 pages, 1597 KiB

Open AccessReview

Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

by Jesús Beltrán-García, Rebeca Osca-Verdegal, Federico V. Pallardó, José Ferreres, María Rodríguez, Sandra Mulet, Fabian Sanchis-Gomar, Nieves Carbonell and José Luis García-Giménez

Antioxidants 2020, 9(10), 936; https://doi.org/10.3390/antiox9100936 - 29 Sep 2020

Cited by 108 | Viewed by 9823

Abstract

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak emerged, countless efforts are being made worldwide to understand the molecular mechanisms underlying the coronavirus disease 2019 (COVID-19) in an attempt to identify the specific clinical characteristics of critically ill COVID-19 patients involved [...] Read more.

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak emerged, countless efforts are being made worldwide to understand the molecular mechanisms underlying the coronavirus disease 2019 (COVID-19) in an attempt to identify the specific clinical characteristics of critically ill COVID-19 patients involved in its pathogenesis and provide therapeutic alternatives to minimize COVID-19 severity. Recently, COVID-19 has been closely related to sepsis, which suggests that most deceases in intensive care units (ICU) may be a direct consequence of SARS-CoV-2 infection-induced sepsis. Understanding oxidative stress and the molecular inflammation mechanisms contributing to COVID-19 progression to severe phenotypes such as sepsis is a current clinical need in the effort to improve therapies in SARS-CoV-2 infected patients. This article aims to review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress and inflammation, which can contribute to sepsis progression. We also provide an overview of potential antioxidant therapies and active clinical trials that might prevent disease progression or reduce its severity. Full article

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

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25 pages, 1014 KiB

Open AccessReview

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

by Ayana Suzumura, Ryo Terao and Hiroki Kaneko

Antioxidants 2020, 9(10), 920; https://doi.org/10.3390/antiox9100920 - 26 Sep 2020

Cited by 27 | Viewed by 3163

Abstract

Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and [...] Read more.

Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and are necessary for homeostasis. They are important retinal membrane components and are involved in energy storage. n-3 fatty acids also have antioxidant and anti-inflammatory properties, and their suppressive effects against ROP, DR, and AMD have been previously evaluated. α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites have been shown to alleviate retinal oxidative stress and inflammation involving various biological signaling pathways. In this review, we summarize the current understanding of the n-3 fatty acids effects on the mechanisms of these retinal diseases and how they exert their therapeutic effects, focusing on ALA, EPA, DHA, and their metabolites. This knowledge may provide new remedial strategies for n-3 fatty acids in the prevention and treatment of retinal diseases associated with oxidative stress and inflammation. Full article

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

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13 pages, 9820 KiB

Open AccessReview

Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma

by Chikako Harada, Takahiko Noro, Atsuko Kimura, Xiaoli Guo, Kazuhiko Namekata, Tadashi Nakano and Takayuki Harada

Antioxidants 2020, 9(9), 874; https://doi.org/10.3390/antiox9090874 - 16 Sep 2020

Cited by 23 | Viewed by 3504

Abstract

Glaucoma is a neurodegenerative disease of the eye, which involves degeneration of retinal ganglion cells (RGCs): the output neurons of the retina to the brain, which with their axons comprise the optic nerve. Recent studies have shown the possible involvement of oxidative stress [...] Read more.

Glaucoma is a neurodegenerative disease of the eye, which involves degeneration of retinal ganglion cells (RGCs): the output neurons of the retina to the brain, which with their axons comprise the optic nerve. Recent studies have shown the possible involvement of oxidative stress in the pathogenesis of glaucoma, especially in the subtype of normal tension glaucoma. Basic experiments utilizing rodent and primate models of glaucoma revealed that antioxidants protect RGCs under various pathological conditions including glutamate neurotoxicity and optic nerve injury. These results suggested that existing drugs and food factors may be useful for prevention and hence therapy of glaucoma. In this review, we highlight some therapeutic candidates, particularly those with antioxidant properties, and discuss the therapeutic potential of RGC protection by modulating gene expressions that prevent and ameliorate glaucoma. Full article

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

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Other

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12 pages, 463 KiB

Open AccessPerspective

Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease

by Lee E. Neilson, Joseph F. Quinn and Nora E. Gray

Antioxidants 2021, 10(1), 28; https://doi.org/10.3390/antiox10010028 - 30 Dec 2020

Cited by 8 | Viewed by 3200

Abstract

Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in [...] Read more.

Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation. Full article

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

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