Antioxidants

21 pages, 3737 KB

Open AccessArticle

Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation

by Zaida Zakaria, Zaidatul Akmal Othman, Joseph Bagi Suleiman, Nur Asyilla Che Jalil, Wan Syaheedah Wan Ghazali, Victor Udo Nna and Mahaneem Mohamed

Antioxidants 2021, 10(12), 2031; https://doi.org/10.3390/antiox10122031 - 20 Dec 2021

Cited by 24 | Viewed by 5626

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight [...] Read more.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis. Full article

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

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14 pages, 324 KB

Open AccessArticle

Olive-Leaf Extracts Modulate Inflammation and Oxidative Stress Associated with Human H. pylori Infection

by Jose Manuel Silvan, Esperanza Guerrero-Hurtado, Alba Gutiérrez-Docio, Teresa Alarcón-Cavero, Marin Prodanov and Adolfo J. Martinez-Rodriguez

Antioxidants 2021, 10(12), 2030; https://doi.org/10.3390/antiox10122030 - 20 Dec 2021

Cited by 23 | Viewed by 5792

Abstract

Helicobacter pylori (H. pylori) is one of the major human pathogens and the main cause of pathological damages that can progress from chronic gastritis to gastric cancer. During the colonization of gastric mucosa, this bacterium provokes a strong inflammatory response and [...] Read more.

Helicobacter pylori (H. pylori) is one of the major human pathogens and the main cause of pathological damages that can progress from chronic gastritis to gastric cancer. During the colonization of gastric mucosa, this bacterium provokes a strong inflammatory response and subsequent oxidative process, which are associated with tissue damage. Therefore, the objective of this research was to evaluate the ability of two olive-leaf extracts (E1 and E2) to modulate the inflammatory response and oxidative stress in H. pylori-infected human gastric AGS cells. The obtained results showed that both extracts significantly decreased interleukin-8 (IL-8) secretion and reactive oxygen species (ROS) production in human gastric AGS cells. Both extracts also showed antibacterial activity against different H. pylori strains. HPLC-PAD-MS characterization demonstrated that extract E1 was mainly composed of highly hydrophilic compounds, such as hydroxytyrosol (HT) and its glucosides, and it was the most effective extract as an antibacterial agent. In contrast, extract E2 was composed mostly of moderately hydrophilic compounds, such as oleuropein (OLE), and it was more effective than extract E1 as an anti-inflammatory agent. Both extracts exhibited similar potential to decrease ROS production. These results show the importance of standardizing the extract composition according to the bioactive properties that should be potentiated. Full article

(This article belongs to the Special Issue Olive Antioxidants: Extraction, Biological Activity and Practical Applications)

20 pages, 3394 KB

Open AccessArticle

Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1^−/− Mice: Impact on Redox Status and Metabolism

by Giulia Bortolussi, Xiaoxia Shi, Lysbeth ten Bloemendaal, Bhaswati Banerjee, Dirk R. De Waart, Gabriele Baj, Weiyu Chen, Ronald P. Oude Elferink, Ulrich Beuers, Coen C. Paulusma, Roland Stocker, Andrés F. Muro and Piter J. Bosma

Antioxidants 2021, 10(12), 2029; https://doi.org/10.3390/antiox10122029 - 20 Dec 2021

Cited by 11 | Viewed by 4053

Abstract

Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact [...] Read more.

Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1^−/− mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra^−/− and Bvra^−/−Ugt1^−/− pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra^−/− and Bvra^−/−Ugt1^−/− mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra^−/− and Bvra^−/−Ugt1^−/− mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra^−/− mice were significantly higher than WT controls, while Bvra^−/−Ugt1^−/− tested normal. The normal parameters observed in Bvra^−/−Ugt1^−/− mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective. Full article

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

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14 pages, 11363 KB

Open AccessReview

Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK

by Verónica Hurtado-Carneiro, Pilar Dongil, Ana Pérez-García, Elvira Álvarez and Carmen Sanz

Antioxidants 2021, 10(12), 2028; https://doi.org/10.3390/antiox10122028 - 20 Dec 2021

Cited by 14 | Viewed by 5993

Abstract

The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is [...] Read more.

The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress. Full article

(This article belongs to the Special Issue Antioxidant Agents for the Prevention and Therapy of Oxidative Stress in Hepatic Diseases)

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20 pages, 20469 KB

Open AccessArticle

A Correlation Study on In Vitro Physiological Activities of Soybean Cultivars, 19 Individual Isoflavone Derivatives, and Genetic Characteristics

by Han-Na Chu, Su-Ji Lee, Xiaohan Wang, Sang-Hoon Lee, Hye-Myeong Yoon, Yu-Jin Hwang, Eun-Suk Jung, Yongseok Kwon, Chi-Do Wee, Kyeong-A Jang and Haeng-Ran Kim

Antioxidants 2021, 10(12), 2027; https://doi.org/10.3390/antiox10122027 - 20 Dec 2021

Cited by 10 | Viewed by 3067

Abstract

The functionality of soybeans is an important factor in the selection and utilization of excellent soybean cultivars, and isoflavones are representative functional substances in soybeans, which exhibit effects on antioxidants, estrogen activity, and cancer, and prevent cardiovascular diseases. This study analyzed ABTS, DPPH, [...] Read more.

The functionality of soybeans is an important factor in the selection and utilization of excellent soybean cultivars, and isoflavones are representative functional substances in soybeans, which exhibit effects on antioxidants, estrogen activity, and cancer, and prevent cardiovascular diseases. This study analyzed ABTS, DPPH, estrogen, ER (ER) alpha, UCP-1, and NO inhibition activities in 48 types of soybean cultivars, as well as the relationship with 19 isolated types of individual isoflavone derivatives. Statistical analysis was conducted to find individual isoflavone derivatives affecting physiological activities, revealing the high correlation of three types of derivatives: genistein 7-O-(6″-O-acetyl)glucoside (6″-O-acetylgenistin), genistein 7-O-(2″-O-apiosyl)glucoside, and glycitein. Based on these results, 15 types of soybean cultivars were selected (one control type, seven yellow types, six black types, and one green type), which have both high physiological activities and a high content of individual isoflavone derivatives. In addition, these high correlations were further verified through a genome-wide association study (GWAS) to determine the association between activities, substances, and genetic characteristics. This study comprehensively describes the relationship between the specific physiological activities of soybean resources, individual isoflavone derivative substances, and SNPs, which will be utilized for in-depth research, such as selection of excellent soybean resources with specific physiological activities. Full article

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11 pages, 1856 KB

Open AccessArticle

Dried Blood Spot Biomarkers of Oxidative Stress and Inflammation Associated with Blood Pressure in Rural Senegalese Women with Incident Hypertension

by Yan Lin, Xiangtian Wang, Luciane Lenz, Ousmane Ndiaye, Jian Qin, Xiaoli Wang, Hui Huang, Marc A. Jeuland and Junfeng Zhang

Antioxidants 2021, 10(12), 2026; https://doi.org/10.3390/antiox10122026 - 20 Dec 2021

Cited by 6 | Viewed by 3574

Abstract

Blood biomarkers of oxidative stress and inflammation have been associated with increased risk of hypertension development; yet their application in sub-Saharan Africa has been limited due to the lack of blood collection facilities. In this study, we evaluated the usefulness of dried blood [...] Read more.

Blood biomarkers of oxidative stress and inflammation have been associated with increased risk of hypertension development; yet their application in sub-Saharan Africa has been limited due to the lack of blood collection facilities. In this study, we evaluated the usefulness of dried blood spots (DBS), a more feasible alternative to venous blood, in rural sub-Saharan residents. We recruited 342 women with incident hypertension from rural Senegal, and measured C-reactive protein (CRP) and malondialdehyde (MDA) in DBS and concurrent blood pressure (BP) at baseline and 1-year follow-up. Associations of DBS biomarkers with current levels of and 1-year changes in BP were examined after adjusting for demographic, medical, and socioeconomic covariates. DBS concentrations of MDA were significantly associated with concurrent systolic BP (SBP) (p < 0.05), while DBS baseline concentrations of CRP were associated with longitudinal changes in SBP between baseline and follow-up. Compared to participants with baseline CRP < 1 mg/L, those with CRP of 1–3 mg/L and 3–10 mg/L had 2.11 mmHg (95%CI: −2.79 to 7.02 mmHg) and 4.68 mmHg (95%CI: 0.01 to 9.36 mmHg) increases in SBP at follow-up, respectively. The results support the use of DBS biomarkers for hypertension prevention and control, especially in settings with limited clinical resources. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative Stress in Acute and Chronic Diseases)

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14 pages, 1467 KB

Open AccessArticle

Linking the Dynamic Changes in the In Vitro Antioxidant Activity of Carob Kibbles upon Roasting to the Chemical and Structural Changes Revealed by FTIR Spectroscopy

by Anna Marina Grigoriou and Eftychia Pinakoulaki

Antioxidants 2021, 10(12), 2025; https://doi.org/10.3390/antiox10122025 - 20 Dec 2021

Cited by 8 | Viewed by 3509

Abstract

Recent studies have highlighted the potential of utilizing carob kibbles as a bioactive-rich food ingredient associated with substantial health benefits. Roasting is a key process in enhancing the sensory characteristics of carob kibbles, also affecting the bioactive polyphenols and leading to the formation [...] Read more.

Recent studies have highlighted the potential of utilizing carob kibbles as a bioactive-rich food ingredient associated with substantial health benefits. Roasting is a key process in enhancing the sensory characteristics of carob kibbles, also affecting the bioactive polyphenols and leading to the formation of Maillard reaction products (MRPs), including the polymeric melanoidins that are associated with a high antioxidant potential but remain unexplored in carob. In this work, we employed for the first time attenuated total reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy to probe the dynamic chemical and structural changes upon the roasting of carob kibbles, along with the investigation of the in vitro antioxidant activity through the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and the determination of the total polyphenolic, proanthocyanidin, gallic acid and cinnamic acid contents. Roasting significantly enhanced the in vitro antioxidant activity of the polyphenolic carob extracts, with different rates at distinct roasting temperatures. The ATR-FTIR analysis enabled the identification of the changes in the structural features of polyphenolic compounds that were related to the improved antioxidant activity upon roasting. Furthermore, the detection of characteristic signatures for the polymeric melanoidins in the infrared (IR) fingerprint region provided the first evidence for the formation and structural properties of these complex, diverse compounds in roasted carob kibbles. Full article

(This article belongs to the Special Issue Bioavailability and Bioactivity of Plant Antioxidants)

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17 pages, 2106 KB

Open AccessArticle

Spatial–Temporal Response of Reactive Oxygen Species and Salicylic Acid Suggest Their Interaction in Pumpkin Rootstock-Induced Chilling Tolerance in Watermelon Plants

by Fei Cheng, Min Gao, Junyang Lu, Yuan Huang and Zhilong Bie

Antioxidants 2021, 10(12), 2024; https://doi.org/10.3390/antiox10122024 - 20 Dec 2021

Cited by 8 | Viewed by 3541

Abstract

Grafting with pumpkin rootstock could improve chilling tolerance in watermelon, and salicylic acid (SA) as a signal molecule is involved in regulating plant tolerance to chilling and other abiotic stresses. To clarify the mechanism in pumpkin rootstock-induced systemic acquired acclimation in grafted watermelon [...] Read more.

Grafting with pumpkin rootstock could improve chilling tolerance in watermelon, and salicylic acid (SA) as a signal molecule is involved in regulating plant tolerance to chilling and other abiotic stresses. To clarify the mechanism in pumpkin rootstock-induced systemic acquired acclimation in grafted watermelon under chilling stress, we used self-grafted (Cl/Cl) and pumpkin rootstock-grafted (Cl/Cm) watermelon seedlings to study the changes in lipid peroxidation, photosystem II (PSII) activity and antioxidant metabolism, the spatio–temporal response of SA biosynthesis and H₂O₂ accumulation to chilling, and the role of H₂O₂ signal in SA-induced chilling tolerance in grafted watermelon. The results showed that pumpkin rootstock grafting promoted SA biosynthesis in the watermelon scions. Chilling induced hydrolysis of conjugated SA into free SA in the roots and accumulation of free SA in the leaves in Cl/Cm plants. Further, pumpkin rootstock grafting induced early response of antioxidant enzyme system in the roots and increased activities of ascorbate peroxidase and glutathione reductase in the leaves, thus maintaining cellular redox homeostasis. Exogenous SA improved while the inhibition of SA biosynthesis reduced chilling tolerance in Cl/Cl seedlings. The application of diphenyleneiodonium (DPI, inhibitor of NADPH oxidase) and dimethylthiourea (DMTU, H₂O₂ scavenger) decreased, while exogenous H₂O₂ improved the PSII activity in Cl/Cl plants under chilling stress. Additionally, the decrease of the net photosynthetic rate in DMTU- and DPI-pretreated Cl/Cl plants under chilling conditions could be alleviated by subsequent application of H₂O₂ but not SA. In conclusion, pumpkin rootstock grafting induces SA biosynthesis and redistribution in the leaves and roots and participates in the regulation of antioxidant metabolism probably through interaction with the H₂O₂ signal, thus improving chilling tolerance in watermelon. Full article

(This article belongs to the Special Issue Plant Redox Biology)

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16 pages, 3332 KB

Open AccessArticle

The Protective Effect of Carotenoids, Polyphenols, and Estradiol on Dermal Fibroblasts under Oxidative Stress

by Aya Darawsha, Aviram Trachtenberg, Joseph Levy and Yoav Sharoni

Antioxidants 2021, 10(12), 2023; https://doi.org/10.3390/antiox10122023 - 20 Dec 2021

Cited by 26 | Viewed by 6830

Abstract

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, induce inflammatory processes in the skin and increase the production of matrix metalloproteinases (MMPs) in dermal fibroblasts, [...] Read more.

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, induce inflammatory processes in the skin and increase the production of matrix metalloproteinases (MMPs) in dermal fibroblasts, which leads to collagen degradation. Several studies have shown the protective role of estrogens and a diet rich in fruits and vegetables on skin physiology. Previous studies have shown that dietary carotenoids and polyphenols activate the cell’s antioxidant defense system by increasing antioxidant response element/Nrf2 (ARE/Nrf2) transcriptional activity and reducing the inflammatory response. The aim of the current study was to examine the protective effect of such dietary-derived compounds and estradiol on dermal fibroblasts under oxidative stress induced by H₂O₂. Human dermal fibroblasts were used to study the effect of H₂O₂ on cell number and apoptosis, MMP-1, and pro-collagen secretion as markers of skin damage. Treatment of cells with H₂O₂ led to cell death, increased secretion of MMP-1, and decreased pro-collagen secretion. Pre-treatment with tomato and rosemary extracts, and with estradiol, reversed the effects of the oxidative stress. This was associated with a reduction in intracellular ROS levels, probably through the measured increased activity of ARE/Nrf2. Conclusions: This study indicates that carotenoids, polyphenols, and estradiol protect dermal fibroblasts from oxidative stress-induced damage through a reduction in ROS levels. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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13 pages, 1293 KB

Open AccessArticle

Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study

by Larissa E. van Eijk, Adriana Tami, Jan-Luuk Hillebrands, Wilfred F. A. den Dunnen, Martin H. de Borst, Peter H. J. van der Voort, Marian L. C. Bulthuis, Alida C. M. Veloo, Karin I. Wold, María F. Vincenti González, Bernardina T. F. van der Gun, Harry van Goor and Arno R. Bourgonje

Antioxidants 2021, 10(12), 2022; https://doi.org/10.3390/antiox10122022 - 20 Dec 2021

Cited by 19 | Viewed by 6231

Abstract

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since [...] Read more.

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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18 pages, 3999 KB

Open AccessArticle

NAD(P)H Drives the Ascorbate–Glutathione Cycle and Abundance of Catalase in Developing Beech Seeds Differently in Embryonic Axes and Cotyledons

by Ewa Marzena Kalemba, Shirin Alipour and Natalia Wojciechowska

Antioxidants 2021, 10(12), 2021; https://doi.org/10.3390/antiox10122021 - 20 Dec 2021

Cited by 5 | Viewed by 3854

Abstract

European beech is an important component of European lowland forests in terms of ecology, and produces irregular seeds categorized as intermediate due to their limited longevity. Removal of the excess of reactive oxygen species is crucial for redox homeostasis in growing plant tissues. [...] Read more.

European beech is an important component of European lowland forests in terms of ecology, and produces irregular seeds categorized as intermediate due to their limited longevity. Removal of the excess of reactive oxygen species is crucial for redox homeostasis in growing plant tissues. Hydrogen peroxide (H₂O₂) is detoxified via the plant-specific ascorbate-glutathione cycle, and enzymatically, mainly by catalase (CAT). The reduced and oxidized (redox) forms of ascorbate (AsA, DHA) and glutathione (GSH, GSSG) decreased during maturation as the content of redox forms of nicotinamide adenine dinucleotide (NADH, NAD⁺) phosphate (NADPH, NADP⁺), cofactors of ascorbate–glutathione enzymes, declined and limited this cycle. The degree of oxidation of glutathione peaked at approximately 80%, at the exact time when the NADP content was the lowest and the NADPH/NADP⁺ ratio reached the highest values. The glutathione pool was reflected in changes in the NADP pool, both in embryonic axes (R² = 0.61) and in cotyledons (R² = 0.98). A large excess of NADPH was reported in embryonic axes, whereas cotyledons displayed more unified levels of NADP redox forms. As a result, anabolic redox charge and reducing power were higher in embryonic axes. CAT was recognized as two proteins, and the abundance of the 55 kDa protein was correlated with all redox forms of ascorbate, glutathione, NAD, and NADP, whereas the 37 kDa protein was oppositely regulated in embryonic axes and cotyledons. Here, we discuss the role of NAD(P) in the regulation of the ascorbate–glutathione cycle, catalase, and seed longevity concerning a putative role of NAD(P)H as a redox biomarker involved in predefining seed quality, because NAD(P)H-derived redox homeostasis was found to be better controlled in embryonic axes than cotyledons. Full article

(This article belongs to the Special Issue NAD⁺ and Pyridine Nucleotides, Central Players in Plant Metabolic and Developmental Acclimation)

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16 pages, 4209 KB

Open AccessArticle

CCN2 Aggravates the Immediate Oxidative Stress–DNA Damage Response following Renal Ischemia–Reperfusion Injury

by Floris A. Valentijn, Sebastiaan N. Knoppert, Georgios Pissas, Raúl R. Rodrigues-Diez, Laura Marquez-Exposito, Roel Broekhuizen, Michal Mokry, Lennart A. Kester, Lucas L. Falke, Roel Goldschmeding, Marta Ruiz-Ortega, Theodoros Eleftheriadis and Tri Q. Nguyen

Antioxidants 2021, 10(12), 2020; https://doi.org/10.3390/antiox10122020 - 20 Dec 2021

Cited by 24 | Viewed by 4427

Abstract

AKI, due to the fact of altered oxygen supply after kidney transplantation, is characterized by renal ischemia–reperfusion injury (IRI). Recent data suggest that AKI to CKD progression may be driven by cellular senescence evolving from prolonged DNA damage response (DDR) following oxidative stress. [...] Read more.

AKI, due to the fact of altered oxygen supply after kidney transplantation, is characterized by renal ischemia–reperfusion injury (IRI). Recent data suggest that AKI to CKD progression may be driven by cellular senescence evolving from prolonged DNA damage response (DDR) following oxidative stress. Cellular communication factor 2 (CCN2, formerly called CTGF) is a major contributor to CKD development and was found to aggravate DNA damage and the subsequent DDR–cellular senescence–fibrosis sequence following renal IRI. We therefore investigated the impact of CCN2 inhibition on oxidative stress and DDR in vivo and in vitro. Four hours after reperfusion, full transcriptome RNA sequencing of mouse IRI kidneys revealed CCN2-dependent enrichment of several signaling pathways, reflecting a different immediate stress response to IRI. Furthermore, decreased staining for γH2AX and p-p53 indicated reduced DNA damage and DDR in tubular epithelial cells of CCN2 knockout (KO) mice. Three days after IRI, DNA damage and DDR were still reduced in CCN2 KO, and this was associated with reduced oxidative stress, marked by lower lipid peroxidation, protein nitrosylation, and kidney expression levels of Nrf2 target genes (i.e., HMOX1 and NQO1). Finally, silencing of CCN2 alleviated DDR and lipid peroxidation induced by anoxia-reoxygenation injury in cultured PTECs. Together, our observations suggest that CCN2 inhibition might mitigate AKI by reducing oxidative stress-induced DNA damage and the subsequent DDR. Thus, targeting CCN2 might help to limit post-IRI AKI. Full article

(This article belongs to the Special Issue Cellular-Redox-Related Stress Responses in Renal Disease and Their Related Complications)

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21 pages, 6505 KB

Open AccessArticle

Essential Oils from Zingiber striolatum Diels Attenuate Inflammatory Response and Oxidative Stress through Regulation of MAPK and NF-κB Signaling Pathways

by Zebin Huang, Lingna Xie, Yongyu Xu, Kai Zhao, Xuetong Li, Jiaben Zhong, Yujing Lu, Xuetao Xu, Susan Goodin, Kun Zhang, Lanyue Zhang, Chunlian Li and Xi Zheng

Antioxidants 2021, 10(12), 2019; https://doi.org/10.3390/antiox10122019 - 19 Dec 2021

Cited by 18 | Viewed by 4825

Abstract

Zingiber striolatum Diels (Z. striolatum), a widely popular vegetable in China, is famous for its medicinal and nutritional values. However, the anti-inflammatory effects of essential oil from Z. striolatum (EOZS) remain unclear. In this study, EOZS from seven regions in China [...] Read more.

Zingiber striolatum Diels (Z. striolatum), a widely popular vegetable in China, is famous for its medicinal and nutritional values. However, the anti-inflammatory effects of essential oil from Z. striolatum (EOZS) remain unclear. In this study, EOZS from seven regions in China were extracted and analyzed by GC–MS. LPS-induced RAW264.7 cells and 12-O-Tetradecanoylphorbol 13-acetate (TPA)-stimulated mice were used to evaluate the anti-inflammatory effects of EOZS. Results show that 116 compounds were identified in EOZS from seven locations. Samples 2, 4 and 5 showed the best capability on DPPH radical scavenging and NO inhibition. They also significantly reduced the production of ROS, pro-inflammatory cytokines, macrophage morphological changes, migration and phagocytic capability. Transcriptomics revealed MAPK and NF-κB signaling pathways may be involved in the anti-inflammatory mechanism, and the predictions were proven by Western blotting. In TPA-induced mice, EOZS reduced the degree of ear swelling and local immune cell infiltration by blocking the activation of MAPK and NF-κB signaling pathways, which was consistent with the in vitro experimental results. Our research unveils the antioxidant capability and potential molecular mechanism of EOZS in regulating inflammatory response, and suggests the application of EOZS as a natural antioxidant and anti-inflammatory agent in the pharmaceutical and functional food industries. Full article

(This article belongs to the Special Issue Antioxidant, Anti-inflammatory and Anticancer Activities of the Natural Products)

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16 pages, 8156 KB

Open AccessArticle

Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects

by Rocío García-Arroyo, Aleix Gavaldà-Navarro, Francesc Villarroya, Gemma Marfany and Serena Mirra

Antioxidants 2021, 10(12), 2018; https://doi.org/10.3390/antiox10122018 - 19 Dec 2021

Cited by 12 | Viewed by 5028

Abstract

The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granules, and mitochondrial metabolism, and it is considered a gene that is resilient [...] Read more.

The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granules, and mitochondrial metabolism, and it is considered a gene that is resilient against oxidative stress in the retina. Mutations in most RP genes affect photoreceptors, but retinal pigment epithelium (RPE) cells may be also altered. Here, we aimed to analyze the effect of CERKL overexpression and depletion in vivo and in vitro, focusing on the state of the mitochondrial network under oxidative stress conditions. Our work indicates that the depletion of CERKL increases the vulnerability of RPE mitochondria, which show a shorter size and altered shape, particularly upon sodium arsenite treatment. CERKL-depleted cells have dysfunctional mitochondrial respiration particularly upon oxidative stress conditions. The overexpression of two human CERKL isoforms (558 aa and 419 aa), which display different protein domains, shows that a pool of CERKL localizes at mitochondria in RPE cells and that CERKL protects the mitochondrial network—both in size and shape—against oxidative stress. Our results support CERKL being a resilient gene that regulates the mitochondrial network in RPE as in retinal neurons and suggest that RPE cell alteration contributes to particular phenotypic traits in patients carrying CERKL mutations. Full article

(This article belongs to the Special Issue Oxidative Stress in the Retina Diseases)

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21 pages, 7376 KB

Open AccessArticle

Biochar and Chitosan Regulate Antioxidant Defense and Methylglyoxal Detoxification Systems and Enhance Salt Tolerance in Jute (Corchorus olitorius L.)

by Mirza Hasanuzzaman, Md. Rakib Hossain Raihan, Ebtihal Khojah, Bassem N. Samra, Masayuki Fujita and Kamrun Nahar

Antioxidants 2021, 10(12), 2017; https://doi.org/10.3390/antiox10122017 - 19 Dec 2021

Cited by 37 | Viewed by 4627

Abstract

We investigated the role of biochar and chitosan in mitigating salt stress in jute (Corchorus olitorius L. cv. O-9897) by exposing twenty-day-old seedlings to three doses of salt (50, 100, and 150 mM NaCl). Biochar was pre-mixed with the soil at 2.0 [...] Read more.

We investigated the role of biochar and chitosan in mitigating salt stress in jute (Corchorus olitorius L. cv. O-9897) by exposing twenty-day-old seedlings to three doses of salt (50, 100, and 150 mM NaCl). Biochar was pre-mixed with the soil at 2.0 g kg⁻¹ soil, and chitosan-100 was applied through irrigation at 100 mg L⁻¹. Exposure to salt stress notably increased lipid peroxidation, hydrogen peroxide content, superoxide radical levels, electrolyte leakage, lipoxygenase activity, and methylglyoxal content, indicating oxidative damage in the jute plants. Consequently, the salt-stressed plants showed reduced growth, biomass accumulation, and disrupted water balance. A profound increase in proline content was observed in response to salt stress. Biochar and chitosan supplementation significantly mitigated the deleterious effects of salt stress in jute by stimulating both non-enzymatic (e.g., ascorbate and glutathione) and enzymatic (e.g., ascorbate peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, glutathione reductase superoxide dismutase, catalase, peroxidase, glutathione S-transferase, glutathione peroxidase) antioxidant systems and enhancing glyoxalase enzyme activities (glyoxalase I and glyoxalase II) to ameliorate reactive oxygen species damage and methylglyoxal toxicity, respectively. Biochar and chitosan supplementation increased oxidative stress tolerance and improved the growth and physiology of salt-affected jute plants, while also significantly reducing Na⁺ accumulation and ionic toxicity and decreasing the Na⁺/K⁺ ratio. These findings support a protective role of biochar and chitosan against salt-induced damage in jute plants. Full article

(This article belongs to the Special Issue Antioxidant Mechanisms in Plants)

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19 pages, 1223 KB

Open AccessArticle

LC-MS Identification and Quantification of Phenolic Compounds in Solid Residues from the Essential Oil Industry

by Maria Irakli, Adriana Skendi, Elisavet Bouloumpasi, Paschalina Chatzopoulou and Costas G. Biliaderis

Antioxidants 2021, 10(12), 2016; https://doi.org/10.3390/antiox10122016 - 19 Dec 2021

Cited by 64 | Viewed by 7575

Abstract

Plant solid residues obtained from the essential oil industry represent a rich source of phenolic compounds with bioactive properties to be used in the food and pharmaceutical industries. A selective and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed for the simultaneous determination [...] Read more.

Plant solid residues obtained from the essential oil industry represent a rich source of phenolic compounds with bioactive properties to be used in the food and pharmaceutical industries. A selective and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed for the simultaneous determination of phenolic compounds in solid residues of the Lamiaceae family plants. A total of 48 compounds can be separated within 35 min by using the Poroshell-120 EC-C₁₈ column, and a gradient mobile phase of 0.1% formic acid and acetonitrile with flow rate of 0.5 mL/min; salicylic acid was used as internal standard. The calibration curves showed good linearity in the tested concentration range for each analyte (R² > 0.9921), while recoveries ranged from 70.1% to 115.0% with an intra-day and inter-day precision of less than 6.63% and 15.00%, respectively. Based on the retention behavior, as well as absorption and mass spectra, 17 phenolic acids, 19 flavonoids and 2 phenolic diterpenes were identified and quantified in the solid residues obtained by distillation of six aromatic plants: oregano, rosemary, sage, satureja, lemon balm, and spearmint. The method constitutes an accurate analytical and quality control tool for the simultaneous quantitation of phenolics present in solid waste residues from the essential oil industry. Full article

(This article belongs to the Special Issue Antioxidants: Sources, Methods, Health Benefits and Industrial Applications)

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16 pages, 2702 KB

Open AccessArticle

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice

by Il-Je Cho, Sung-Eon Kim, Beom-Rak Choi, Hye-Rim Park, Jeong-Eun Park, Seong-Hwa Hong, Young-Sam Kwon, Won-Seok Oh and Sae-Kwang Ku

Antioxidants 2021, 10(12), 2015; https://doi.org/10.3390/antiox10122015 - 19 Dec 2021

Cited by 11 | Viewed by 4515

Abstract

Lemon balm and corn silk are valuable medicinal herbs, which exhibit variety of beneficial effects for human health. The present study explored the anti-obesity effects of a mixture of lemon balm and corn silk extracts (M-LB/CS) by comparison with the effects of single [...] Read more.

Lemon balm and corn silk are valuable medicinal herbs, which exhibit variety of beneficial effects for human health. The present study explored the anti-obesity effects of a mixture of lemon balm and corn silk extracts (M-LB/CS) by comparison with the effects of single herbal extracts in high-fat diet (HFD)-induced obesity in mice. HFD supplementation for 84 days increased the body weight, the fat mass density, the mean diameter of adipocytes, and the thickness of fat pads. However, oral administration of M-LB/CS significantly alleviated the HFD-mediated weight gain and adipocyte hypertrophy without affecting food consumption. Of the various combination ratios of M-LB/CS tested, the magnitude of the decreases in weight gain and adipocyte hypertrophy by administration of 1:1, 1:2, 2:1, and 4:1 (w/w) M-LB/CS was more potent than that by single herbal extracts alone. In addition, M-LB/CS reduced the HFD-mediated increases in serum cholesterol, triglyceride, and low-density lipoprotein, prevented the reduction in serum high-density lipoprotein, and facilitated fecal excretion of cholesterol and triglyceride. Moreover, M-LB/CS mitigated the abnormal changes in specific mRNAs associated with lipogenesis and lipolysis in the adipose tissue. Furthermore, M-LB/CS reduced lipid peroxidation by inhibiting the HFD-mediated reduction in glutathione, catalase, and superoxide dismutase. Therefore, M-LB/CS is a promising herbal mixture for preventing obesity. Full article

(This article belongs to the Special Issue Flavonoids and Chronic Diseases)

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30 pages, 493 KB

Open AccessReview

Flavonoids Present in Propolis in the Battle against Photoaging and Psoriasis

by Claudia Rebeca Rivera-Yañez, Porfirio Alonso Ruiz-Hurtado, María Isabel Mendoza-Ramos, Julia Reyes-Reali, Gina Stella García-Romo, Glustein Pozo-Molina, Aldo Arturo Reséndiz-Albor, Oscar Nieto-Yañez, Adolfo René Méndez-Cruz, Claudia Fabiola Méndez-Catalá and Nelly Rivera-Yañez

Antioxidants 2021, 10(12), 2014; https://doi.org/10.3390/antiox10122014 - 19 Dec 2021

Cited by 26 | Viewed by 6570

Abstract

The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the [...] Read more.

The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient’s health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches. Full article

(This article belongs to the Special Issue Flavonoids and Chronic Diseases)

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8 pages, 517 KB

Open AccessArticle

Innovative Blood Antioxidant Test in Standardbred Trotter Horses

by Raffaella Rossi, Chiara Maria Lo Feudo, Enrica Zucca, Francesco Vizzarri, Carlo Corino and Francesco Ferrucci

Antioxidants 2021, 10(12), 2013; https://doi.org/10.3390/antiox10122013 - 18 Dec 2021

Cited by 4 | Viewed by 2685

Abstract

In athletic horses, prolonged and intense training gives rise to an imbalance between the production of free radicals and antioxidant molecules, leading to oxidative stress. Considering the relation between exercise and oxidative stress in horses, the present work aims to validate the Kit [...] Read more.

In athletic horses, prolonged and intense training gives rise to an imbalance between the production of free radicals and antioxidant molecules, leading to oxidative stress. Considering the relation between exercise and oxidative stress in horses, the present work aims to validate the Kit Radicaux Libres (KRL) test as a tool to verify the influence of taming, training and racing on the total blood antioxidant activity and some haematochemical parameters. Five Italian Standardbred racehorses (two males and three females, aged 12 ± 1 months) from the same training center were selected and monitored upon arrival and during the following year until the racing season. Blood samples were obtained at different timepoints, corresponding to different steps of training. The data showed that KRL values were higher (p < 0.001) before the beginning of the taming period and at 60 days of taming, compared with the training and racing periods; additionally, the total protein value was affected by the training program, whereas no effects of training on muscle enzymes were detected. These results confirm that exercise plays a role in the production of free radicals and show that the KRL test may represent a valid method to determine oxidative stress in athletic horses. Full article

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25 pages, 930 KB

Open AccessReview

Free Radicals and Neonatal Brain Injury: From Underlying Pathophysiology to Antioxidant Treatment Perspectives

by Silvia Martini, Laura Castellini, Roberta Parladori, Vittoria Paoletti, Arianna Aceti and Luigi Corvaglia

Antioxidants 2021, 10(12), 2012; https://doi.org/10.3390/antiox10122012 - 18 Dec 2021

Cited by 26 | Viewed by 5385

Abstract

Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles [...] Read more.

Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles of injury have been identified. The growing evidence on the detrimental effects of free radicals on the brain tissue has led to discover not only potential biomarkers for oxidative damage, but also possible neuroprotective therapeutic approaches targeting oxidative stress. While a more extensive validation of free radical biomarkers is required before considering their use in routine neonatal practice, two important treatments endowed with antioxidant properties, such as therapeutic hypothermia and magnesium sulfate, have become part of the standard of care to reduce the risk of neonatal brain injury, and other promising therapeutic strategies are being tested in clinical trials. The implementation of currently available evidence is crucial to optimize neonatal neuroprotection and to develop individualized diagnostic and therapeutic approaches addressing oxidative brain injury, with the final aim of improving the neurological outcome of this population. Full article

(This article belongs to the Special Issue Oxidative Stress in Newborns and Children)

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16 pages, 6583 KB

Open AccessArticle

Umuhengerin Neuroprotective Effects in Streptozotocin-Induced Alzheimer’s Disease Mouse Model via Targeting Nrf2 and NF-Kβ Signaling Cascades

by Alaa Sirwi, Nesrine S. El Sayed, Hossam M. Abdallah, Sabrin R. M. Ibrahim, Gamal A. Mohamed, Ali M. El-Halawany, Martin K. Safo and Nora O. Abdel Rasheed

Antioxidants 2021, 10(12), 2011; https://doi.org/10.3390/antiox10122011 - 18 Dec 2021

Cited by 20 | Viewed by 4318

Abstract

Alzheimer’s disease (AD) is the most common type of dementia and is characterized by advanced cognitive deterioration, deposition of Aβ (amyloid-beta), and the formation of neurofibrillary tangles. Administration of streptozotocin (STZ) via the intracerebroventricular (ICV) route is a reliable model resembling sporadic AD [...] Read more.

Alzheimer’s disease (AD) is the most common type of dementia and is characterized by advanced cognitive deterioration, deposition of Aβ (amyloid-beta), and the formation of neurofibrillary tangles. Administration of streptozotocin (STZ) via the intracerebroventricular (ICV) route is a reliable model resembling sporadic AD (SAD) associated neuropathological changes. The present study was undertaken to explore the neuroprotective effects of the methoxy flavonoid, umuhengerin, in an STZ-induced SAD mouse model as a potential therapy for AD. Mice were injected once with STZ (3 mg/kg, ICV), followed by daily administration of umuhengerin (orally, 30 mg/kg) or the positive control donepezil (orally, 2.5 mg/kg) for 21 days. The pharmacological activity of umuhengerin was assessed through estimation of oxidative stress and inflammatory markers via mouse ELISA kits, Western blot analysis, and brain histopathological examination. Morris water maze test was also conducted to investigate umuhengerin-induced cognitive enhancement. The results showed that umuhengerin attenuated STZ-produced neuroinflammation and oxidative stress with a notable rise in the expression of Nrf2 (nuclear factor erythroid 2-related factor 2). In contrast, it downregulated Keap-1 (Kelch-like ECH associated protein 1), as well as elevated brain contents of GSH (reduced glutathione) and HO-1 (heme oxygenase-1). STZ-injected animals receiving umuhengerin showed marked downregulation of the nuclear factor kappa beta (NF-Kβp65) and noticeable increment in the expression of its inhibitor kappa beta alpha protein (IKβα), as well as prominent reduction in malondialdehyde (MDA), H₂O₂ (hydrogen peroxide), and TNF-α (tumor-necrosis factor-alpha) contents. Β-secretase protein expression and acetylcholinesterase (AchE) activity were also diminished upon umuhengerin injection in the STZ group, leading to decreased Aβ formation and cognitive improvement, respectively. In conclusion, umuhengerin neuroprotective effects were comparable to the standard drug donepezil; thus, it could be an alternative approach for AD management. Full article

(This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurological and Neurodegenerative Disorders)

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16 pages, 3389 KB

Open AccessArticle

AMPK-PINK1/Parkin Mediated Mitophagy Is Necessary for Alleviating Oxidative Stress-Induced Intestinal Epithelial Barrier Damage and Mitochondrial Energy Metabolism Dysfunction in IPEC-J2

by Shuting Cao, Hao Xiao, Xin Li, Jiang Zhu, Jingchun Gao, Li Wang and Caihong Hu

Antioxidants 2021, 10(12), 2010; https://doi.org/10.3390/antiox10122010 - 18 Dec 2021

Cited by 45 | Viewed by 5698

Abstract

The imbalance of redox biology and oxidative stress leads to intestinal barrier injury and mitophagy. However, much uncertainty still exists about the role of mitophagy in oxidative stress and intestinal function. Here, we showed the effects of hydrogen peroxide (H₂O₂ [...] Read more.

The imbalance of redox biology and oxidative stress leads to intestinal barrier injury and mitophagy. However, much uncertainty still exists about the role of mitophagy in oxidative stress and intestinal function. Here, we showed the effects of hydrogen peroxide (H₂O₂)-induced oxidative stress on intestinal epithelial cell oxidation balance, intestinal barrier function and mitochondrial energy metabolism and its underlying mechanism. In this study, we found that H₂O₂-induced oxidative stress activated adenosine monophosphate-activated protein kinase (AMPK) and enhanced mitophagy in intestinal porcine epithelial cells (IPEC-J2). While compound C (AMPK inhibitor) and mdivi-1 (mitophagy inhibitor) significantly reduced the activity of superoxide dismutase (SOD) and increased mitochondrial reactive oxygen species (ROS) levels in H₂O₂ treated cells. Moreover, compound C and mdivi-1 significantly reduced the trans-epithelium electrical resistant (TER) and increased the fluorescein isothiocyanate-dextran (FD4) flux in H₂O₂ treated IPEC-J2. Furthermore, compound C and mdivi-1 significantly reduced the activity of mitochondrial complex II. Seahorse XF96 data showed that compound C + mdivi-1+ H₂O₂ treatment significantly reduced maximum respiratory oxygen consumption and spare respiratory capacity. Additionally, compound C or mdivi-1 treatment reduced the formation of mitochondrial autophagosomes. These results unveiled that AMPK and PINK1/Parkin mediated mitophagy is necessary for alleviating oxidative stress induced intestinal epithelial barrier damage and mitochondrial energy metabolism dysfunction in IPEC-J2. Full article

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17 pages, 3180 KB

Open AccessArticle

The Effects of Sorbus aucuparia L. Fruit Extracts on Oxidative/Nitrative Modifications of Human Fibrinogen, Impact on Enzymatic Properties of Thrombin, and Hyaluronidase Activity In Vitro

by Magdalena Rutkowska, Joanna Kolodziejczyk-Czepas and Monika Anna Olszewska

Antioxidants 2021, 10(12), 2009; https://doi.org/10.3390/antiox10122009 - 18 Dec 2021

Cited by 5 | Viewed by 3384

Abstract

Sorbus aucuparia L. fruits (rowanberries) are food products with acknowledged nutritional value, high phenolic content, and traditional application in diabetes. In this study, the effects of rowanberry extracts (phytochemically standardised, i.a., by LC-MS/MS) on some aspects of plasma haemostasis and vascular conditions were [...] Read more.

Sorbus aucuparia L. fruits (rowanberries) are food products with acknowledged nutritional value, high phenolic content, and traditional application in diabetes. In this study, the effects of rowanberry extracts (phytochemically standardised, i.a., by LC-MS/MS) on some aspects of plasma haemostasis and vascular conditions were evaluated in vitro as possible mechanisms connected with cardiovascular complications of diabetes. The analyses of structural modifications of human fibrinogen under oxidative stress conditions (C-ELISA, SDS-PAGE and Western blot) revealed that the extracts (at a concentration of 1–5 µg/mL) considerably reduced the nitration of tyrosine residues and formation of high-molecular-weight aggregates. Moreover, they inhibited the enzymatic activity of thrombin (both amidolytic and proteolytic). Additionally, some promising outcomes might be expected regarding endothelial functions from the extracts ability to inhibit hyaluronidase. Parallel experiments on model polyphenols and correlation studies formed the basis for determining the contribution of different compounds, including hydroxycinnamic acid derivatives, flavonols, and low- or high-molecular-weight flavan-3-ols derivatives (proanthocyanidins), to the observed effects. The possible synergistic activity of individual constituents was also noticed. These results broaden the knowledge on the biological activity of rowanberries, partly confirming their health-promoting properties, and indicating that their functional applications might be promising. Full article

(This article belongs to the Special Issue Antioxidants in Foods II)

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30 pages, 2038 KB

Open AccessSystematic Review

Non-Invasive Measurement of Exercise-Induced Oxidative Stress in Response to Physical Activity. A Systematic Review and Meta-Analysis

by Giulia Squillacioti, Fulvia Guglieri, Nicoletta Colombi, Federica Ghelli, Paola Berchialla, Paolo Gardois and Roberto Bono

Antioxidants 2021, 10(12), 2008; https://doi.org/10.3390/antiox10122008 - 17 Dec 2021

Cited by 7 | Viewed by 4391

Abstract

Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses [...] Read more.

Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses including the most frequently quantified biomarkers of oxidative stress, namely, urinary isoprostane and DNA oxidation products, were performed. Three electronic databases (PubMed, EMBASE and Cochrane CENTRAL) were interrogated. Among 4479 records, 43 original articles were included in the systematic review and 11 articles were included in meta-analysis I and II, respectively. We observed a pooled trend of increase of urinary isoprostanes in response to physical activity (+0.95, 95% CI: −0.18; 2.09). In comparison with aerobic exercise, anaerobic training determined a greater induction of isoprostanes (+5.21, 95% CI: 2.76; 7.66, p < 0.0001), which were markedly increased after vigorous physical activity (+6.01, 95% CI: 1.18; 10.84, p < 0.001) and slightly decreased in response to exercise interventions protracted over time (e.g., months) (−1.19, 95% CI: −2.25; −0.12, p < 0.001). We recommend the most integrative approach of oxidative stress multi-marker panels in response to physical activity instead of selecting one preferential biomarker to quantify physical activity-induced oxidative stress in humans. Full article

(This article belongs to the Topic Redox Metabolism)

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15 pages, 1707 KB

Open AccessArticle

An Intercellular Flow of Glutathione Regulated by Interleukin 6 Links Astrocytes and the Liver in the Pathophysiology of Amyotrophic Lateral Sclerosis

by Rafael López-Blanch, Rosario Salvador-Palmer, José M. Estrela and Elena Obrador

Antioxidants 2021, 10(12), 2007; https://doi.org/10.3390/antiox10122007 - 16 Dec 2021

Cited by 8 | Viewed by 3026

Abstract

Oxidative stress has been proposed as a major mechanism of damage to motor neurons associated with the progression of amyotrophic lateral sclerosis (ALS). Astrocytes are the most numerous glial cells in the central nervous system and, under physiological conditions, protect neurons from oxidative [...] Read more.

Oxidative stress has been proposed as a major mechanism of damage to motor neurons associated with the progression of amyotrophic lateral sclerosis (ALS). Astrocytes are the most numerous glial cells in the central nervous system and, under physiological conditions, protect neurons from oxidative damage. However, it is uncertain how their reactive phenotype may affect motor neurons during ALS progression. In two different ALS mouse models (SOD1^G93A and FUS-R521C), we found that increased levels of proinflammatory interleukin 6 facilitate glutathione (GSH) release from the liver to blood circulation, which can reach the astrocytes and be channeled towards motor neurons as a mechanism of antioxidant protection. Nevertheless, although ALS progression is associated with an increase in GSH efflux from astrocytes, generation of reactive oxygen species also increases, suggesting that as the disease progresses, astrocyte-derived oxidative stress could be key to motor-neuron damage. Full article

(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)

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14 pages, 24755 KB

Open AccessArticle

Antioxidants into Nopal (Opuntia ficus-indica), Important Inhibitors of Free Radicals’ Formation

by Romina Castañeda-Arriaga, Adriana Perez-Gonzalez, Tiziana Marino, Nino Russo and Annia Galano

Antioxidants 2021, 10(12), 2006; https://doi.org/10.3390/antiox10122006 - 16 Dec 2021

Cited by 13 | Viewed by 3909

Abstract

Nopal (Opuntia ficus indica) belonging to the Cactacea family has many nutritional benefits attributed to a wide variety of phenolic and flavonoid compounds. Coumaric acid (COA), ferulic acid (FLA), protocatechuic acid (PRA), and gallic acid (GAA) are the phenolic acids (PhAs) [...] Read more.

Nopal (Opuntia ficus indica) belonging to the Cactacea family has many nutritional benefits attributed to a wide variety of phenolic and flavonoid compounds. Coumaric acid (COA), ferulic acid (FLA), protocatechuic acid (PRA), and gallic acid (GAA) are the phenolic acids (PhAs) present in nopal. In this study, the role of these PhAs in copper-induced oxidative stress was investigated using the density functional theory (DFT). The PhAs form 5 thermodynamically favorable complexes with Cu(II), their conditional Gibbs free energies of reaction (ΔG’, at pH = 7.4, in kcal/mol) are from −23 kcal/mol to −18 kcal/mol. All of them are bi-dentate complexes. The complexes of PRA and GAA are capable of inhibiting the Cu(II) reduction by both O₂^•− and Asc⁻, their reactions with the chelated metal are endergonic having rate constants about ~10⁻⁵–10² M⁻¹ s⁻¹, PhAs can prevent the formation of hydroxyl free radicals by chelating the copper ions. Once the hydroxyl radicals are formed by Fenton reactions, the complexes of PhAs with Cu(II) can immediately react with them, thus inhibiting the damage that they can cause to molecules of biological interest. The reactions between PhAs-Cu(II) complexes and hydroxyl free radical were estimated to be diffusion-limited (~10⁸ M⁻¹s⁻¹). Thus, these chelates can reduce the harmful effects caused by the most reactive free radical existent immediately after it is formed by Fenton reactions. Full article

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14 pages, 3069 KB

Open AccessArticle

Low Dietary n6/n3 Ratio Attenuates Changes in the NRF 2 Gene Expression, Lipid Peroxidation, and Inflammatory Markers Induced by Fructose Overconsumption in the Rat Abdominal Adipose Tissue

by Petra Roškarić, Marcela Šperanda, Tomislav Mašek, Donatella Verbanac and Kristina Starčević

Antioxidants 2021, 10(12), 2005; https://doi.org/10.3390/antiox10122005 - 16 Dec 2021

Cited by 11 | Viewed by 3007

Abstract

The objective of this study was to examine the benefits of different n6/n3 polyunsaturated fatty acid ratios on the lipid metabolism, insulin resistance, and oxidative stress in the adipose tissue of rats fed a high-fructose diet. Male and female rats were divided into [...] Read more.

The objective of this study was to examine the benefits of different n6/n3 polyunsaturated fatty acid ratios on the lipid metabolism, insulin resistance, and oxidative stress in the adipose tissue of rats fed a high-fructose diet. Male and female rats were divided into four groups: a control group (CON) (n6/n3 ratio ~7), a high-fructose group (HF) (n6/n3 ratio ~7), an N6-HF group (n6/n3 ratio ~50), and the DHA-HF group (n6/n3 ratio ~1, with the addition of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid). The CON group received plain water and the HF group received 15% fructose in their drinking water. Fructose induced an increase in the content of serum triglycerides, serum cholesterol, and HOMA-IR index. Among the fatty acids, elevated proportions of C18:1n9 and C16:1n7, as well as an increase in total monounsaturated fatty acid (MUFA), were found in the adipose tissue of the HF group. Fructose treatment also changed oxidative parameters, including a marked increase in the serum malondialdehyde (MDA) content. Meanwhile, DHA supplementation caused a significant decrease in the serum MDA concentration in comparison with the HF group. In addition, DHA/EPA supplementation attenuated oxidative stress by increasing NRF 2 gene expression. Fructose treatment also significantly decreased the adiponectin level, while DHA supplementation ameliorated it. The changes observed in this trial, including the decrease in the content of DHA and EPA, the decreased EPA/ARA ratio, and the increase in the expression of inflammatory genes, are characteristics of the low-grade inflammation caused by fructose treatment. These changes in the rat adipose tissue could be prevented by dietary intervention consisting of DHA supplementation and a low n6/n3 ratio. Full article

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15 pages, 4420 KB

Open AccessReview

Fermentation Affects the Antioxidant Activity of Plant-Based Food Material through the Release and Production of Bioactive Components

by Yan-Sheng Zhao, Aya Samy Eweys, Jia-Yan Zhang, Ying Zhu, Juan Bai, Osama M. Darwesh, Hai-Bo Zhang and Xiang Xiao

Antioxidants 2021, 10(12), 2004; https://doi.org/10.3390/antiox10122004 - 16 Dec 2021

Cited by 176 | Viewed by 9494

Abstract

This review reports on the effects of fermentation on the chemical constituents and antioxidant activity of plant-based food materials. Fermentation involves a series of reactions that modify the chemical components of the substrate. It could be considered a tool to increase the bioactive [...] Read more.

This review reports on the effects of fermentation on the chemical constituents and antioxidant activity of plant-based food materials. Fermentation involves a series of reactions that modify the chemical components of the substrate. It could be considered a tool to increase the bioactive compounds and functional properties of food plant materials. Oxidative damage is key to the progression of many human diseases, and the production of antioxidant compounds by fermentation will be helpful to reduce the risk of these diseases. Fermentation also can improve antioxidant activity given its association with increased phytochemicals, antioxidant polysaccharides, and antioxidant peptides produced by microbial hydrolysis or biotransformation. Additionally, fermentation can encourage the breakdown of plant cell walls, which helps to liberate or produce various antioxidant compounds. Overall, results indicated that fermentation in many cases contributed to enhancing antioxidants’ content and antioxidant capacity, supporting the fermentation use in the production of value-added functional food. This review provides an overview of the factors that impact the effects of fermentation on bioactive compound composition and antioxidant activity. The impacts of fermentation are summarized as a reference to its effects on food plant material. Full article

(This article belongs to the Special Issue Natural Products: Biological-, Antioxidant Properties and Health Effects)

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22 pages, 3272 KB

Open AccessArticle

LC-MS/HRMS Analysis, Anti-Cancer, Anti-Enzymatic and Anti-Oxidant Effects of Boerhavia diffusa Extracts: A Potential Raw Material for Functional Applications

by Kouadio Ibrahime Sinan, Uğur Akpulat, Afaf A. Aldahish, Yasemin Celik Altunoglu, Mehmet Cengiz Baloğlu, Dimitrina Zheleva-Dimitrova, Reneta Gevrenova, Devina Lobine, Mohamad Fawzi Mahomoodally, Ouattara Katinan Etienne, Gokhan Zengin, Shafi Mahmud and Raffaele Capasso

Antioxidants 2021, 10(12), 2003; https://doi.org/10.3390/antiox10122003 - 16 Dec 2021

Cited by 45 | Viewed by 6419

Abstract

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An [...] Read more.

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation. Full article

(This article belongs to the Special Issue Natural Compounds from Plants with Antioxidant Properties)

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14 pages, 2157 KB

Open AccessArticle

Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome

by Chiara Caselli, Raffaele De Caterina, Rosetta Ragusa, Riccardo Liga, Alessia Gimelli, Arthur J. H. A. Scholte, Aldo Clerico, Juhani Knuuti and Danilo Neglia

Antioxidants 2021, 10(12), 2002; https://doi.org/10.3390/antiox10122002 - 15 Dec 2021

Cited by 3 | Viewed by 3040

Abstract

Background. The NF-E2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients [...] Read more.

Background. The NF-E2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients with chronic coronary syndromes (CCS). Methods. HO-1 was measured in 526 patients (60 ± 9 years, 318 males) with CCS. Coronary computed tomography angiography (CTA) and stress imaging were used to assess the disease phenotype (coronary atherosclerosis and myocardial ischemia) in a subgroup of 347 patients. Results. In the overall population, HO-1 median value (25–75 percentile) was 5.195 (1.75–8.25) ng/mL. Patients with higher HO-1 were more frequently male, had a higher BMI and lower LVEF%, but otherwise similar risk factors than the other patients. Their bio-humoral profile was characterized by higher markers of endothelial/myocardial dysfunction, but lower levels of cholesterol lipoproteins. Coronary artery disease was characterized by more diffuse atherosclerosis, with mainly non-obstructive and calcified plaques, and a higher prevalence of functional ischemia. Conclusion: In patients with CCS, higher plasma HO-1 levels are associated with lower cholesterol and a more diffuse but mainly non-obstructive coronary atherosclerosis, confirming a potential role for the Nrf2/HO-1 pathway as a protective feedback. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: A Mutual Relationship in Cardiometabolic Diseases)

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Antioxidants, Volume 10, Issue 12 (December 2021) – 175 articles

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