Antioxidants

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Open AccessCommunication

Profiling of Polyphenol Composition and Antiradical Capacity of Erica cinerea

by Alfredo Aires and Rosa Carvalho

Antioxidants 2017, 6(3), 72; https://doi.org/10.3390/antiox6030072 - 20 Sep 2017

Cited by 2 | Viewed by 4410

The aim of the current study was to determine the profile and content of polyphenols present in Erica cinerea, an important plant species from Northern Portuguese flora and often reported as having anti-inflammatory, antioxidant, and anti-radical activity. The analysis of polyphenols was [...] Read more.

The aim of the current study was to determine the profile and content of polyphenols present in Erica cinerea, an important plant species from Northern Portuguese flora and often reported as having anti-inflammatory, antioxidant, and anti-radical activity. The analysis of polyphenols was performed by HPLC-DAD/UV-Vis, and the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) method was used to evaluate its radical scavenging activity. HPLC analysis showed that both plants presented a great diversity of compounds, with 33% flavones, 28% flavanols, and 26% hydroxycinnamic acids. The antiradical activity was dose-dependent, and the IC₅₀ values were 0.251 mg mL⁻¹. Based on our study, E. cinerea presented interesting bioactive compounds and it can be used to extract and purify bioactive polyphenols to be used in pharmaceutical or agro-food industries. Full article

(This article belongs to the Special Issue Bioactive Phenolic Compounds)

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Open AccessReview

Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review

by Zheng Feei Ma and Hongxia Zhang

Antioxidants 2017, 6(3), 71; https://doi.org/10.3390/antiox6030071 - 15 Sep 2017

Cited by 128 | Viewed by 17041

Abstract

Grapes are one of the most widely grown fruits and have been used for winemaking since the ancient Greek and Roman civilizations. Grape seeds are rich in proanthocyanidins which have been shown to possess potent free radical scavenging activity. Grape seeds are a [...] Read more.

Grapes are one of the most widely grown fruits and have been used for winemaking since the ancient Greek and Roman civilizations. Grape seeds are rich in proanthocyanidins which have been shown to possess potent free radical scavenging activity. Grape seeds are a complex matrix containing 40% fiber, 16% oil, 11% proteins, and 7% complex phenols such as tannins. Grape seeds are rich sources of flavonoids and contain monomers, dimers, trimers, oligomers, and polymers. The monomeric compounds includes (+)-catechins, (−)-epicatechin, and (−)-epicatechin-3-O-gallate. Studies have reported that grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Their potential health benefits include protection against oxidative damage, and anti-diabetic, anti-cholesterol, and anti-platelet functions. Recognition of such health benefits of proanthocyanidins has led to the use of grape seeds as a dietary supplement by the consumers. This paper summarizes the studies of the phytochemical compounds, pharmacological properties, and industrial applications of grape seeds. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Prevention of Non-Communicable Diseases)

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Open AccessReview

Antioxidant Activity of Spices and Their Impact on Human Health: A Review

by Alexander Yashin, Yakov Yashin, Xiaoyan Xia and Boris Nemzer

Antioxidants 2017, 6(3), 70; https://doi.org/10.3390/antiox6030070 - 15 Sep 2017

Cited by 321 | Viewed by 32199

Abstract

Antioxidants are substances that prevent oxidation of other compounds or neutralize free radicals. Spices and herbs are rich sources of antioxidants. They have been used in food and beverages to enhance flavor, aroma and color. Due to their excellent antioxidant activity, spices and [...] Read more.

Antioxidants are substances that prevent oxidation of other compounds or neutralize free radicals. Spices and herbs are rich sources of antioxidants. They have been used in food and beverages to enhance flavor, aroma and color. Due to their excellent antioxidant activity, spices and herbs have also been used to treat some diseases. In this review article, the chemical composition and antioxidant activity of spices and culinary herbs are presented. The content of flavonoids and total polyphenols in different spices and herbs are summarized. The applications of spices and their impacts on human health are briefly described. The extraction and analytical methods for determination of antioxidant capacity are concisely reviewed. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Health Promotion)

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Open AccessArticle

A Possible Indicator of Oxidative Damage in Smokers: (13Z)-Lycopene?

by Daniel L. Graham, Mario Lorenz, Andrew J. Young and Gordon M. Lowe

Antioxidants 2017, 6(3), 69; https://doi.org/10.3390/antiox6030069 - 13 Sep 2017

Cited by 3 | Viewed by 4959

Abstract

In vitro, the gaseous phase of cigarette smoke is known to induce both isomerization and degradation of dietary carotenoids, such as β-carotene and lycopene. However, the effects of cigarette smoke on the composition of circulating lycopene in vivo are not well understood. In [...] Read more.

In vitro, the gaseous phase of cigarette smoke is known to induce both isomerization and degradation of dietary carotenoids, such as β-carotene and lycopene. However, the effects of cigarette smoke on the composition of circulating lycopene in vivo are not well understood. In this study, we examined the lycopene profiles of plasma from non-smokers and smokers. No oxidative intermediates of lycopene that have been observed previously in vitro were detected in the plasma, but evidence of isomerization of the carotenoid was seen. Four geometric forms of lycopene were detected in the plasma of both smokers and non-smokers, namely the (5Z), (9Z), (13Z) and (all-E) forms. The relative amounts of these isomers differed between the two cohorts and there was a significant difference (p < 0.05) between smokers and non-smokers for the ratio of total-Z:all-E lycopene, and in the relative amounts of (13Z) and (all-E)-lycopene. The ratio of (all-E):(13Z)-lycopene was 0.84:1.00 in smokers compared to 1.04:1.00 in non-smokers. In smokers, the (13Z)-isomer was generated in preference to the more thermodynamically stable (5Z) and (9Z)-isomers. This mirrors the scenario seen in vitro, in which the formation of (13Z)-lycopene was the main isomer that accompanied the depletion of (all-E) lycopene, when exposed to cigarette smoke. The results suggest that the relative amount of (13Z)-lycopene could be used as an indicator of oxidative damage to lycopene in vivo. Full article

(This article belongs to the Special Issue Carotenoids—Antioxidant Properties)

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Open AccessArticle

Solanum trilobatum L. Ameliorate Thioacetamide-Induced Oxidative Stress and Hepatic Damage in Albino Rats

by Kumar Ganesan, Kumeshini Sukalingam and Baojun Xu

Antioxidants 2017, 6(3), 68; https://doi.org/10.3390/antiox6030068 - 22 Aug 2017

Cited by 35 | Viewed by 8797

Abstract

Solanum trilobatum L. (Solanaceae) has been well known as nightshade, commonly used by diverse populations to heal several disorders. Earlier studies in Solanum trilobatum were focused on different pharmacological activities and a few were concerned with antioxidant and hepatoprotective effects. Thus, the current [...] Read more.

Solanum trilobatum L. (Solanaceae) has been well known as nightshade, commonly used by diverse populations to heal several disorders. Earlier studies in Solanum trilobatum were focused on different pharmacological activities and a few were concerned with antioxidant and hepatoprotective effects. Thus, the current study was focused to evaluate the antioxidant potential and hepatoprotective effects of S. trilobatum L. on thioacetamide (TAA) intoxication in Wistar albino rats. The rats were kept into four groups and six animals each. Group A was normal control. Group B was the TAA treated control. Groups C and D were pretreated with the aqueous extract from the leaves of S. trilobatum (100 mg, 200 mg/kg bw p.o.) once daily for 10 consecutive days administration followed by a single dose infusion of TAA (100 mg/kg s.c.). After 10 days, blood and livers were collected. The biochemical assay was carried out in the GSH (reduced glutathione), TBARS(thiobarbituric acid reactive substances), Na⁺-K⁺-ATPase, and antioxidant enzymes viz., SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase), GST (glutathione-S-transferase), and GR (glutathione reductase) were analyzed in samples of blood and liver. Treatment with S. trilobatum reduced blood and liver TBARS, and Na⁺ K⁺ ATPase activity in TAA (thioacetamide)-induced hepatotoxicity rats. Furthermore, the above antioxidant enzymes were increased in the pretreatment of S. trilobatum in TAA intoxicated rats. Finally, we concluded that S. Trilobatum displayed potent antioxidant properties and alleviate oxidative stress induced hepatotoxic effects and possible engross mechanisms related to free radical scavenging properties. Full article

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Open AccessArticle

Development of a Rapid Method for the Determination of Caffeine in Coffee Grains by GC-FID—A Fully Validated Approach

by Ioannis N. Pasias, I. Kiriakou and Charalampos Proestos

Antioxidants 2017, 6(3), 67; https://doi.org/10.3390/antiox6030067 - 22 Aug 2017

Cited by 11 | Viewed by 6410

Abstract

A simple method for the determination of caffeine in coffee grains by GC-FID (Gas Chromatography-Flame Ionisation Detector) is presented in the current work. The method was fully validated according to ISO (International Organization for Standardization) 17025 requirements and European Commission regulations. The accuracy, [...] Read more.

A simple method for the determination of caffeine in coffee grains by GC-FID (Gas Chromatography-Flame Ionisation Detector) is presented in the current work. The method was fully validated according to ISO (International Organization for Standardization) 17025 requirements and European Commission regulations. The accuracy, as provided by recovery experiments, was higher than 93%, and the precision, as provided by the (%) relative standard deviation under reproducibility conditions, was lower than 5%. A vast number of independent parameters that lead in the increase of uncertainty of methods were investigated. The analysis was performed without use of an internal standard, which was proven to be reliable according to several validation methods. The method was applied in real samples, and possible health claims were investigated. Full article

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Open AccessReview

Superoxide Dismutases in Pancreatic Cancer

by Justin G. Wilkes, Matthew S. Alexander and Joseph J. Cullen

Antioxidants 2017, 6(3), 66; https://doi.org/10.3390/antiox6030066 - 19 Aug 2017

Cited by 18 | Viewed by 8704

Abstract

The incidence of pancreatic cancer is increasing as the population ages but treatment advancements continue to lag far behind. The majority of pancreatic cancer patients have a K-ras oncogene mutation causing a shift in the redox state of the cell, favoring malignant [...] Read more.

The incidence of pancreatic cancer is increasing as the population ages but treatment advancements continue to lag far behind. The majority of pancreatic cancer patients have a K-ras oncogene mutation causing a shift in the redox state of the cell, favoring malignant proliferation. This mutation is believed to lead to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and superoxide overproduction, generating tumorigenic behavior. Superoxide dismutases (SODs) have been studied for their ability to manage the oxidative state of the cell by dismuting superoxide and inhibiting signals for pancreatic cancer growth. In particular, manganese superoxide dismutase has clearly shown importance in cell cycle regulation and has been found to be abnormally low in pancreatic cancer cells as well as the surrounding stromal tissue. Likewise, extracellular superoxide dismutase expression seems to favor suppression of pancreatic cancer growth. With an increased understanding of the redox behavior of pancreatic cancer and key regulators, new treatments are being developed with specific targets in mind. This review summarizes what is known about superoxide dismutases in pancreatic cancer and the most current treatment strategies to be advanced from this knowledge. Full article

(This article belongs to the Special Issue Superoxide Dismutase (SOD) Enzymes, Mimetics and Oxygen Radicals)

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Open AccessReview

Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?

by Jeffrey R. Liddell

Antioxidants 2017, 6(3), 65; https://doi.org/10.3390/antiox6030065 - 18 Aug 2017

Cited by 139 | Viewed by 13077

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis [...] Read more.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis are characterised by oxidative stress, Nrf2 is commonly activated in these diseases. Evidence demonstrates that Nrf2 activity is repressed in neurons in vitro, and only cultured astrocytes respond strongly to Nrf2 inducers, leading to the interpretation that Nrf2 signalling is largely restricted to astrocytes. However, Nrf2 activity can be observed in neurons in post-mortem brain tissue and animal models of disease. Thus this interpretation may be false, and a detailed analysis of the cell type expression of Nrf2 in neurodegenerative diseases is required. This review describes the evidence for Nrf2 activation in each cell type in prominent neurodegenerative diseases and normal aging in human brain and animal models of neurodegeneration, the response to pharmacological and genetic modulation of Nrf2, and clinical trials involving Nrf2-modifying drugs. Full article

(This article belongs to the Special Issue Astrocyte Antioxidant Systems)

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Open AccessArticle

Analysis and Comparison of the Antioxidant Component of Portulaca Oleracea Leaves Obtained by Different Solid-Liquid Extraction Techniques

by Monica Gallo, Esterina Conte and Daniele Naviglio

Antioxidants 2017, 6(3), 64; https://doi.org/10.3390/antiox6030064 - 12 Aug 2017

Cited by 36 | Viewed by 7987

Abstract

Portulaca oleracea is a wild plant pest of orchards and gardens, but is also an edible vegetable rich in beneficial nutrients. It possesses many antioxidant properties due to the high content of vitamins, minerals, omega-3 essential fatty acids and other healthful compounds; therefore, [...] Read more.

Portulaca oleracea is a wild plant pest of orchards and gardens, but is also an edible vegetable rich in beneficial nutrients. It possesses many antioxidant properties due to the high content of vitamins, minerals, omega-3 essential fatty acids and other healthful compounds; therefore, the intake of purslane and/or its bioactive compounds could help to improve the health and function of the whole human organism. Accordingly, in this work it was analyzed and compared to the extractive capacity of the antioxidant component of purslane leaves obtained by solid-liquid extraction techniques such as: hot-maceration, maceration with ultrasound, rapid solid-liquid dynamic extraction using the Naviglio extractor, and a combination of two techniques (mix extraction). The chromatographic analysis by High Performance Liquid Chromatography (HPLC) of the methanolic extract of dried purslane leaves allowed the identification of various polyphenolic compounds for comparison with the standards. In addition, the properties of the different extracts were calculated on dry matter and the antioxidant properties of the total polyphenol components analyzed by the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. The results showed that mix extraction was the most efficient compared to other techniques. In fact, it obtained a quantity of polyphenols amounting to 237.8 mg Gallic Acid Equivalents (GAE)/100 g of fresh weight, while in other techniques, the range varied from 60–160 mg GAE/100 g fresh weight. In addition, a qualitative analysis by Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS) of the phenolic compounds present in the purslane leaves examined was carried out. The compounds were identified by comparison of their molecular weight, fragmentation pattern and retention time with those of standards, using the “Multiple Reaction Monitoring” mode (MRM). Therefore, this study allowed the re-evaluation of a little-known plant that possesses as its beneficial properties, a great potential for use in both the food and the nutraceuticals and cosmetic field. Full article

(This article belongs to the Special Issue Extraction of Antioxidants: Innovative and Intensification Methods, Activity Enhancement and Degradations)

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Open AccessReview

The Ability of Exercise-Associated Oxidative Stress to Trigger Redox-Sensitive Signalling Responses

by Richard Webb, Michael G. Hughes, Andrew W. Thomas and Keith Morris

Antioxidants 2017, 6(3), 63; https://doi.org/10.3390/antiox6030063 - 10 Aug 2017

Cited by 50 | Viewed by 7801

Abstract

In this review, we discuss exercise as an oxidative stressor, and elucidate the mechanisms and downstream consequences of exercise-induced oxidative stress. Reactive oxygen species (ROS) are generated in the mitochondria of contracting skeletal myocytes; also, their diffusion across the myocyte membrane allows their [...] Read more.

In this review, we discuss exercise as an oxidative stressor, and elucidate the mechanisms and downstream consequences of exercise-induced oxidative stress. Reactive oxygen species (ROS) are generated in the mitochondria of contracting skeletal myocytes; also, their diffusion across the myocyte membrane allows their transport to neighbouring muscle tissue and to other regions of the body. Although very intense exercise can induce oxidative damage within myocytes, the magnitudes of moderate-intensity exercise-associated increases in ROS are quite modest (~two-fold increases in intracellular and extracellular ROS concentrations during exercise), and so the effects of such increases are likely to involve redox-sensitive signalling effects rather than oxidative damage. Therefore, the responses of muscle and non-muscle cells to exercise-associated redox-sensitive signalling effects will be reviewed; for example, transcription factors such as Peroxisome Proliferator Activated Receptor-gamma (PPARγ) and Liver X-Receptor-alpha (LXRα) comprise redox-activable signalling systems, and we and others have reported exercise-associated modulation of PPARγ and/or LXRα-regulated genes in skeletal myocyte and in non-muscle cell-types such as monocyte-macrophages. Finally, the consequences of such responses in the context of management of chronic inflammatory conditions, and also their implications for the design of exercise training programmes (particularly the use of dietary antioxidants alongside exercise), will be discussed. Full article

(This article belongs to the Special Issue Exercise Induced Muscle Damage and Oxidative Stress)

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Open AccessReview

Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes

by Gethin J. McBean

Antioxidants 2017, 6(3), 62; https://doi.org/10.3390/antiox6030062 - 3 Aug 2017

Cited by 126 | Viewed by 19308

Abstract

This review discusses the current understanding of cysteine and glutathione redox balance in astrocytes. Particular emphasis is placed on the impact of oxidative stress and astrocyte activation on pathways that provide cysteine as a precursor for glutathione. The effect of the disruption of [...] Read more.

This review discusses the current understanding of cysteine and glutathione redox balance in astrocytes. Particular emphasis is placed on the impact of oxidative stress and astrocyte activation on pathways that provide cysteine as a precursor for glutathione. The effect of the disruption of thiol-containing amino acid metabolism on the antioxidant capacity of astrocytes is also discussed. Full article

(This article belongs to the Special Issue Astrocyte Antioxidant Systems)

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Open AccessArticle

Fate and Prediction of Phenolic Secoiridoid Compounds throughout the Different Stages of the Virgin Olive Oil Making Process

by Giuseppe Fregapane and M. Desamparados Salvador

Antioxidants 2017, 6(3), 61; https://doi.org/10.3390/antiox6030061 - 3 Aug 2017

Cited by 10 | Viewed by 4781

Abstract

The evolution of the main phenolic secoiridoid compounds throughout the different stages of the virgin olive oil making process—crushing, malaxation and liquid-solid separation—is studied here, with the goal of making possible the prediction of the partition and transformation that take place in the [...] Read more.

The evolution of the main phenolic secoiridoid compounds throughout the different stages of the virgin olive oil making process—crushing, malaxation and liquid-solid separation—is studied here, with the goal of making possible the prediction of the partition and transformation that take place in the different steps of the process. The concentration of hydroxytyrosol secoiridoids produced under the different crushing conditions studied are reasonably proportional to the intensity of the milling stage, and strongly depend on the olive variety processed. During malaxation, the content of the main phenolic secoiridoids is reduced, especially in the case of the hydroxytyrosol derivatives, in which a variety-dependent behaviour is observed. The prediction of the concentration of phenolic secoiridoids finally transferred from the kneaded paste to the virgin olive oil is also feasible, and depends on the phenolic content and amount of water in the olive paste. The determination of the phenolic compounds in the olive fruit, olive paste and olive oil has been carried out by LC-MS (Liquid-Chromatography Mass-Spectrometry). This improved knowledge could help in the use of more adequate processing conditions for the production of virgin olive oil with desired properties; for example, higher or lower phenolic content, as the amount of these minor components is directly related to its sensory, antioxidant and healthy properties. Full article

(This article belongs to the Special Issue Bioactive Phenolic Compounds)

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Open AccessArticle

Fractioning of Proanthocyanidins of Uncaria tomentosa. Composition and Structure-Bioactivity Relationship

by Mirtha Navarro, William Zamora, Silvia Quesada, Gabriela Azofeifa, Diego Alvarado and Maria Monagas

Antioxidants 2017, 6(3), 60; https://doi.org/10.3390/antiox6030060 - 28 Jul 2017

Cited by 16 | Viewed by 6702

Abstract

In a previous study, the detailed low-molecular weight polyphenolic profile of the different plant parts (leaves, stem, bark and wood) of Uncaria tomentosa was reported, the leaves being the plant part with the highest phenolic content and presenting the most heterogenous proanthocyanidin composition. [...] Read more.

In a previous study, the detailed low-molecular weight polyphenolic profile of the different plant parts (leaves, stem, bark and wood) of Uncaria tomentosa was reported, the leaves being the plant part with the highest phenolic content and presenting the most heterogenous proanthocyanidin composition. Further, cytotoxicity of leaves extracts in two cancer cell lines was also found to be higher than in the remaining parts of the plant. In the present study, fractioning of U. tomentosa leaves polyphenolic extracts was performed using Diaion^® HP-20 resin and a detailed characterization and quantification of fractions (n = 5) was achieved using advanced analytical techniques such as Ultra-Performance Liquid Chromatography coupled with Electrospray Ionization and Triple Quadrupole (TQD) Tandem Mass Spectrometry (UPLC/TQ-ESI-MS) and ¹³C-NMR. Oxygen Radical Absorbance Capacity (ORAC) and cytotoxicity on gastric adenocarcinoma AGS and colon adenocarcinoma SW20 cell lines were also determined in the different fractions. Results showed selective distribution of 32 non-flavonoid and flavonoid phenolics among the different fractions. ORAC varied between 3.2 and 11.8 μmol TE/mg in the different fractions, whereas IC₅₀ of cytotoxicity on gastric adenocarcinoma AGS and colon adenocarcinoma SW20 cell lines best values were between 71.4 and 75.6 µg/mL. Fractions rich in proanthocyanidins also showed the highest bioactivity. In fact, significant positive correlation was found between total proanthocyanidins (TP) quantified by UPLC-DAD and ORAC (R² = 0.970), whereas significant negative correlation was found between TP and cytotoxicity towards AGS (R² = 0.820) and SW620 (R² = 0.843) adenocarcinoma cell lines. Among proanthocyanidins, propelargonidin dimers were of particular interest, showing significant correlation with cytotoxic selectivity on both gastric AGS (R² = 0.848) and colon SW620 (R² = 0.883) adenocarcinoma cell lines. These results show further evidence of the bioactivity of U. tomentosa proanthocyanidin extracts and their potential health effects. Full article

(This article belongs to the Special Issue Bioactive Phenolic Compounds)

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Open AccessArticle

Storage of Fruits and Vegetables in Refrigerator Increases their Phenolic Acids but Decreases the Total Phenolics, Anthocyanins and Vitamin C with Subsequent Loss of their Antioxidant Capacity

by Joseph H. Y. Galani, Jalpesh S. Patel, Nilesh J. Patel and Jayant G. Talati

Antioxidants 2017, 6(3), 59; https://doi.org/10.3390/antiox6030059 - 24 Jul 2017

Cited by 90 | Viewed by 13208

Abstract

It is of paramount importance for consumers, scientists and industrialists to understand how low-temperature storage of food items affects their bioactive compounds and properties. This study evaluated the effects of cold storage on total phenolics (TP), phenolic acids profile (PA), total anthocyanins (TA), [...] Read more.

It is of paramount importance for consumers, scientists and industrialists to understand how low-temperature storage of food items affects their bioactive compounds and properties. This study evaluated the effects of cold storage on total phenolics (TP), phenolic acids profile (PA), total anthocyanins (TA), total ascorbic acid (Vit. C) and antioxidant activity (AA) of 19 fruits and vegetables, collected from local Indian markets and stored in refrigerator (4 °C) during 15 days. Content of TP was highest in dill and amaranth and decreased (up to 29.67%) with storage. Leafy vegetables (amaranth, dill, onion, fenugreek and spinach) contained higher amounts of the 12 PA revealed by UPLC-UV; ellagic, gallic, sinapic and vanillic acids levels were the highest; chlorogenic acid (ρ = 0.423), syringic acid (ρ = 0.403) and sinapic acid (ρ = 0.452) mostly correlated with TP; and the PA increased during storage. Highest contents of Vit C estimated by AOAC, DCPIP and DNP methods were found in amaranth, dill and pomegranate, and decreased with storage. Pomegranate showed highest TA levels and low-temperature storage did not significantly increase TA, which was the largest contributor of TP in fruits and vegetables (ρ = 0.661). Storage induced a drastic decrease of AA, which mostly correlated with TP (ρ = 0.808, 0.690 and 0.458 for DPPH, ABTS and FRAP assays, respectively). Spearman’s correlation confirmed by principal component analysis demonstrated that dill, pomegranate and amaranth had the highest overall antioxidant capacity, whereas orange juice and carrot showed the lowest. The results provide support for a key-role of TP, followed by Vit. C and TA in antioxidant capacity of fruits and vegetables, which could be interesting dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress. Full article

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Open AccessArticle

High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells

by Maria Leticia Castro, Georgia M. Carson, Melanie J. McConnell and Patries M. Herst

Antioxidants 2017, 6(3), 58; https://doi.org/10.3390/antiox6030058 - 22 Jul 2017

Cited by 18 | Viewed by 5466

Abstract

We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated [...] Read more.

We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H₂O₂ in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H₂O₂ treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H₂O₂ treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway. Full article

(This article belongs to the Special Issue Vitamin C: Current Concepts in Human Physiology)

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Open AccessArticle

Chemical Analysis of Astragali Complanati Semen and Its Hypocholesterolemic Effect Using Serum Metabolomics Based on Gas Chromatography-Mass Spectrometry

by Tung Ting Sham, Huan Zhang, Daniel Kam Wah Mok, Shun Wan Chan, Jianhong Wu, Songyun Tang and Chi On Chan

Antioxidants 2017, 6(3), 57; https://doi.org/10.3390/antiox6030057 - 21 Jul 2017

Cited by 11 | Viewed by 6727

Abstract

The hypocholesterolemic protective effect of the dried seed of Astragalus complanatus (ACS) was investigated in rats fed with normal diet, high cholesterol diet (HCD), and HCD plus 70% ethanol extract of ACS (600 mg/kg/day) by oral gavage for four weeks. ACS extract was [...] Read more.

The hypocholesterolemic protective effect of the dried seed of Astragalus complanatus (ACS) was investigated in rats fed with normal diet, high cholesterol diet (HCD), and HCD plus 70% ethanol extract of ACS (600 mg/kg/day) by oral gavage for four weeks. ACS extract was tested to be rich in antioxidants, which may be contributed to its high content of phenolic compounds. Consumption of ACS remarkably suppressed the elevated total cholesterol (p < 0.01) and LDL-C (p < 0.001) induced by HCD. Chemical constituents of ACS extract were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization orbitrap mass spectrometry and the results showed that the ACS extract mainly consisted of phenolic compounds including flavonoids and flavonoid glycosides. In addition, based on the serum fatty acid profiles, elucidated using gas chromatography-mass spectrometry, free and esterified fatty acids including docosapentaenoic acid, adrenic acid, dihomo-γ-linolenic acid and arachidonic acid were regulated in ACS treatment group. Western blot results further indicated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) (p < 0.05) in liver was upregulated in ACS treatment group. To conclude, our results clearly demonstrated that ACS provides beneficial effect on lowering HCD associated detrimental change. Full article

(This article belongs to the Special Issue Bioactive Phenolic Compounds)

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Open AccessReview

NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease

by Pradeep Manuneedhi Cholan, Siân P. Cartland and Mary M. Kavurma

Antioxidants 2017, 6(3), 56; https://doi.org/10.3390/antiox6030056 - 12 Jul 2017

Cited by 10 | Viewed by 7245

Abstract

Peripheral artery disease (PAD) is caused by narrowing of arteries in the limbs, normally occurring in the lower extremities, with severe cases resulting in amputation of the foot or leg. A potential approach for treatment is to stimulate the formation of new blood [...] Read more.

Peripheral artery disease (PAD) is caused by narrowing of arteries in the limbs, normally occurring in the lower extremities, with severe cases resulting in amputation of the foot or leg. A potential approach for treatment is to stimulate the formation of new blood vessels to restore blood flow to limb tissues. This is a process called angiogenesis and involves the proliferation, migration, and differentiation of endothelial cells. Angiogenesis can be stimulated by reactive oxygen species (ROS), with NADPH oxidases (NOX) being a major source of ROS in endothelial cells. This review summarizes the recent evidence implicating NOX isoforms in their ability to regulate angiogenesis in vascular endothelial cells in vitro, and in PAD in vivo. Increasing our understanding of the involvement of the NOX isoforms in promoting therapeutic angiogenesis may lead to new treatment options to slow or reverse PAD. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

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Open AccessArticle

Attenuation of Red Blood Cell Storage Lesions with Vitamin C

by Kimberly Sanford, Bernard J. Fisher, Evan Fowler, Alpha A. Fowler and Ramesh Natarajan

Antioxidants 2017, 6(3), 55; https://doi.org/10.3390/antiox6030055 - 12 Jul 2017

Cited by 19 | Viewed by 8740

Abstract

Stored red blood cells (RBCs) undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as “storage lesions”. We hypothesized that vitamin C (VitC, reduced or oxidized) would reduce red cell storage lesions, thus prolonging their storage duration. [...] Read more.

Stored red blood cells (RBCs) undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as “storage lesions”. We hypothesized that vitamin C (VitC, reduced or oxidized) would reduce red cell storage lesions, thus prolonging their storage duration. Whole-blood-derived, leuko-reduced, SAGM (saline-adenine-glucose-mannitol)-preserved RBC concentrates were equally divided into four pediatric storage bags and the following additions made: (1) saline (saline); (2) 0.3 mmol/L reduced VitC (Lo VitC); (3) 3 mmol/L reduced VitC (Hi VitC); or (4) 0.3 mmol/L oxidized VitC (dehydroascorbic acid, DHA) as final concentrations. Biochemical and rheological parameters were serially assessed at baseline (prior to supplementation) and Days 7, 21, 42, and 56 for RBC VitC concentration, pH, osmotic fragility by mechanical fragility index, and percent hemolysis, LDH release, glutathione depletion, RBC membrane integrity by scanning electron microscopy, and Western blot for β-spectrin. VitC exposure (reduced and oxidized) significantly increased RBC antioxidant status with varying dynamics and produced trends in reduction in osmotic fragility and increases in membrane integrity. Conclusion: VitC partially protects RBC from oxidative changes during storage. Combining VitC with other antioxidants has the potential to improve long-term storage of RBC. Full article

(This article belongs to the Special Issue Vitamin C: Current Concepts in Human Physiology)

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Open AccessReview

Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

by Fereshteh Ahmadinejad, Simon Geir Møller, Morteza Hashemzadeh-Chaleshtori, Gholamreza Bidkhori and Mohammad-Saeid Jami

Antioxidants 2017, 6(3), 51; https://doi.org/10.3390/antiox6030051 - 10 Jul 2017

Cited by 213 | Viewed by 16161

Abstract

Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, [...] Read more.

Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinson’s disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1). Although they share the targets in reversing the cytotoxic effects of H₂O₂, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis. Full article

(This article belongs to the Special Issue Antioxidant and Neuroprotection)

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Antifungal and Antiochratoxigenic Activities of Essential Oils and Total Phenolic Extracts: A Comparative Study

by Rachelle EL Khoury, Ali Atoui, Florence Mathieu, Hiba Kawtharani, Anthony EL Khoury, Richard G. Maroun and Andre EL Khoury

Antioxidants 2017, 6(3), 44; https://doi.org/10.3390/antiox6030044 - 9 Jul 2017

Cited by 18 | Viewed by 5834

Abstract

This study is intended to prevent ochratoxin A (OTA) production by Aspergillus carbonarius S402 using essential oils (EOs) and total phenolic compounds extracted from plants and herbs. The EOs used in this study are the following: bay leaves, cumin, fenugreek, melissa, mint, and [...] Read more.

This study is intended to prevent ochratoxin A (OTA) production by Aspergillus carbonarius S402 using essential oils (EOs) and total phenolic compounds extracted from plants and herbs. The EOs used in this study are the following: bay leaves, cumin, fenugreek, melissa, mint, and sage. As for the phenolic compounds, they were extracted from bay leaves, cumin, fenugreek, melissa, mint, sage, anise, chamomile, fennel, rosemary, and thyme. The experiments were conducted on Synthetic Grape Medium (SGM) medium at 28 °C for 4 days. OTA was extracted from the medium with methanol and quantified using HPLC (High Performance Liquid Chromatography). Results showed that EOs had a greater impact than the total phenolic extracts on the OTA production. Reduction levels ranged between 25% (sage) and 80% (melissa) for the EOs at 5 µL mL⁻¹, and 13% (thyme) and 69% (mint) for the phenolic extracts. Although they did not affect the growth of A. carbonarius, total phenolic extracts and EOs were capable of partially reducing OTA production. Reduction levels depended on the nature of the plants and the concentration of the EOs. Reducing OTA with natural extracts could be a solution to prevent OTA production without altering the fungal growth, thus preserving the natural microbial balance. Full article

(This article belongs to the Special Issue Bioactive Phenolic Compounds)

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Open AccessReview

Reactive Oxygen and Nitrogen Species in the Development of Pulmonary Hypertension

by David J.R. Fulton, Xueyi Li, Zsuzsanna Bordan, Stephen Haigh, Austin Bentley, Feng Chen and Scott A. Barman

Antioxidants 2017, 6(3), 54; https://doi.org/10.3390/antiox6030054 - 6 Jul 2017

Cited by 64 | Viewed by 9876

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature that involves the loss of endothelial function together with inappropriate smooth muscle cell growth, inflammation, and fibrosis. These changes underlie a progressive remodeling of blood vessels that alters flow and increases [...] Read more.

Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature that involves the loss of endothelial function together with inappropriate smooth muscle cell growth, inflammation, and fibrosis. These changes underlie a progressive remodeling of blood vessels that alters flow and increases pulmonary blood pressure. Elevated pressures in the pulmonary artery imparts a chronic stress on the right ventricle which undergoes compensatory hypertrophy but eventually fails. How PAH develops remains incompletely understood and evidence for the altered production of reactive oxygen and nitrogen species (ROS, RNS respectively) in the pulmonary circulation has been well documented. There are many different types of ROS and RNS, multiple sources, and collective actions and interactions. This review summarizes past and current knowledge of the sources of ROS and RNS and how they may contribute to the loss of endothelial function and changes in smooth muscle proliferation in the pulmonary circulation. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

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Open AccessReview

Possible Reactions of Dietary Phenolic Compounds with Salivary Nitrite and Thiocyanate in the Stomach

by Umeo Takahama and Sachiko Hirota

Antioxidants 2017, 6(3), 53; https://doi.org/10.3390/antiox6030053 - 5 Jul 2017

Cited by 26 | Viewed by 6030

Abstract

Foods are mixed with saliva in the oral cavity and swallowed. While staying in the stomach, saliva is contentiously provided to mix with the ingested foods. Because a salivary component of nitrite is protonated to produce active nitrous acid at acidic pH, the [...] Read more.

Foods are mixed with saliva in the oral cavity and swallowed. While staying in the stomach, saliva is contentiously provided to mix with the ingested foods. Because a salivary component of nitrite is protonated to produce active nitrous acid at acidic pH, the redox reactions of nitrous acid with phenolic compounds in foods become possible in the stomach. In the reactions, nitrous acid is reduced to nitric oxide (•NO), producing various products from phenolic compounds. In the products, stable hydroxybezoyl benzofuranone derivatives, which are produced from quercetin and its 7-O-glucoside, are included. Caffeic acid, chlorogenic acid, and rutin are oxidized to quinones and the quinones can react with thiocyanic acid derived from saliva, producing stable oxathiolone derivatives. 6,8-Dinitrosocatechis are produced from catechins by the redox reaction, and the dinitrocatechins are oxidized further by nitrous acid producing the quinones, which can make charge transfer complexes with the dinitrosocatechin and can react with thiocyanic acid producing the stable thiocyanate conjugates. In this way, various products can be produced by the reactions of salivary nitrite with dietary phenolic compounds, and reactive and toxic quinones formed by the reactions are postulated to be removed in the stomach by thiocyanic acid derived from saliva. Full article

(This article belongs to the Special Issue Bioactive Phenolic Compounds)

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Open AccessArticle

Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells

by Hong-Quan Duong, Kyu Sic You, Seunghoon Oh, Sahng-June Kwak and Yeon-Sun Seong

Antioxidants 2017, 6(3), 52; https://doi.org/10.3390/antiox6030052 - 1 Jul 2017

Cited by 57 | Viewed by 8269

Abstract

Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug [...] Read more.

Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy. We aimed to evaluate the possibility that modulation of NRF2 expression could be effective in the treatment of pancreatic cancer cells. We investigated whether the depletion of NRF2 by using small interfering RNAs (siRNAs) is effective in the expression of biomarkers of pancreatic cancer stemness such as aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1). NRF2 knockdown markedly reduced the expression of NRF2 and glutamate-cysteine ligase catalytic subunit (GCLC) in cell lines established from pancreatic cancers. NRF2 silencing also decreased the ALDH1A1 and ALDH3A1 expression. Furthermore, this NRF2 depletion enhanced the antiproliferative effects of the chemotherapeutic agent, 5-fluorouracil (5-FU) in pancreatic cancer cells. Full article

(This article belongs to the Special Issue Oxidative Stress and Cancer: The Nrf2 Enigma)

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Antioxidant Activity of Yichun Blue Honeysuckle (YBHS) Berry Counteracts CCl₄-Induced Toxicity in Liver Injury Model of Mice

by Mian-Ying Wang, Madhuwanti Srinivasan, Subramanyam Dasari, Parnal Narvekar, Angela Lincy Prem Antony Samy, Venkata Satish Dontaraju, Lin Peng, Gary L. Anderson and Gnanasekar Munirathinam

Antioxidants 2017, 6(3), 50; https://doi.org/10.3390/antiox6030050 - 30 Jun 2017

Cited by 17 | Viewed by 6620

Abstract

Yichun Blue Honeysuckle (YBHS) is reported to have a broad range of health benefits including protection against a number of chronic diseases. The objective of our study was to determine whether YBHS exhibits antioxidant activity, and if so, determine how it provides protection [...] Read more.

Yichun Blue Honeysuckle (YBHS) is reported to have a broad range of health benefits including protection against a number of chronic diseases. The objective of our study was to determine whether YBHS exhibits antioxidant activity, and if so, determine how it provides protection against oxidative stress. Eight-week old mice (25 male and 25 female) were randomized into five groups (n = 10 per group). YBHS extract (at 6.25%, 12.5%, or 25%) was administrated via intra-gastric tube to mice at 0.1 mL/10 g body weight once daily for 7 days. On the 8th day, all animals except for the controls received 250 mg/kg of CCl₄ through an intra-gastric tube. The animals were sacrificed 6 h after CCl₄ administration. Liver samples obtained from these mice were analyzed for the levels of Thiobarbituric Acid Reactive Substances (TBARS) and glutathione and the activities of Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPx), using biochemical assay kits. Our results showed that YBHS indeed reduces lipid peroxidation, suggesting that YBHS decreases the Reactive Oxygen Species (ROS) levels. We also found that YBHS activated the endogenous antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase and its co-enzyme glutathione reductase. In addition, we showed that glutathione levels were increased by YBHS treatment. Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealed that YBHS has potent free radical scavenging activity. Based on the results from our study, we conclude that YBHS scavenges ROS by enhancing the activity of the endogenous antioxidant defense system activity for conferring liver protective effects. Full article

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Open AccessReview

Vitamin C and Microvascular Dysfunction in Systemic Inflammation

by Karel Tyml

Antioxidants 2017, 6(3), 49; https://doi.org/10.3390/antiox6030049 - 29 Jun 2017

Cited by 42 | Viewed by 7996

Abstract

Sepsis, life-threatening organ dysfunction caused by a dysfunctional host response to infection, is associated with high mortality. A promising strategy to improve the outcome is to inject patients intravenously with ascorbate (vitamin C). In animal models of sepsis, this injection improves survival and, [...] Read more.

Sepsis, life-threatening organ dysfunction caused by a dysfunctional host response to infection, is associated with high mortality. A promising strategy to improve the outcome is to inject patients intravenously with ascorbate (vitamin C). In animal models of sepsis, this injection improves survival and, among others, the microvascular function. This review examines our recent work addressing ascorbate’s ability to inhibit arteriolar dysfunction and capillary plugging in sepsis. Arteriolar dysfunction includes impaired vasoconstriction/dilation (previously reviewed) and impaired conduction of vasoconstriction/dilation along the arteriole. We showed that ascorbate injected into septic mice prevents impaired conducted vasoconstriction by inhibiting neuronal nitric oxide synthase-derived NO, leading to restored inter-endothelial electrical coupling through connexin 37-containing gap junctions. Hypoxia/reoxygenation (confounding factor in sepsis) also impairs electrical coupling by protein kinase A (PKA)-dependent connexin 40 dephosphorylation; ascorbate restores PKA activation required for this coupling. Both effects of ascorbate could explain its ability to protect against hypotension in sepsis. Capillary plugging in sepsis involves P-selectin mediated platelet-endothelial adhesion and microthrombi formation. Early injection of ascorbate prevents capillary plugging by inhibiting platelet-endothelial adhesion and endothelial surface P-selectin expression. Ascorbate also prevents thrombin-induced platelet aggregation and platelet surface P-selectin expression, thus preventing microthrombi formation. Delayed ascorbate injection reverses capillary plugging and platelet-endothelial adhesion; it also attenuates sepsis-induced drop in platelet count in systemic blood. Thrombin-induced release of plasminogen-activator-inhibitor-1 from platelets (anti-fibrinolytic event in sepsis) is inhibited by ascorbate pH-dependently. Thus, under acidotic conditions in sepsis, ascorbate promotes dissolving of microthrombi in capillaries. We propose that protected/restored arteriolar conduction and capillary bed perfusion by ascorbate contributes to reduced organ injury and improved survival in sepsis. Full article

(This article belongs to the Special Issue Vitamin C: Current Concepts in Human Physiology)

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Open AccessArticle

Early and Late Induction of KRAS and HRAS Proto-Oncogenes by Reactive Oxygen Species in Primary Astrocytes

by Samantha Messina, Erika Di Zazzo and Bruno Moncharmont

Antioxidants 2017, 6(3), 48; https://doi.org/10.3390/antiox6030048 - 29 Jun 2017

Cited by 8 | Viewed by 4807

Abstract

Astrocytes, one of the predominant types of glial cells, function as both supportive and metabolic cells for the brain. Among mammalian tissues, the highest levels of p21^Ras protein are detected in the brain. Here, we investigated the expression of KRAS and HRAS [...] Read more.

Astrocytes, one of the predominant types of glial cells, function as both supportive and metabolic cells for the brain. Among mammalian tissues, the highest levels of p21^Ras protein are detected in the brain. Here, we investigated the expression of KRAS and HRAS proto-oncogenes in primary astrocytes following acute oxidative stimulation. Reactive oxygen species (ROS) changed the expression of proto-oncogenes at both transcriptional and translational levels. De novo protein synthesis analysis measured approximate values of proteins half-life, ranging from 1–4 h, of the different H- and K- isoforms by western blot analysis. Quantitative gene expression analysis of KRAS and HRAS revealed an unexpected short-term induction of KRAS mRNA in primary astrocytes in response to acute stimulation. Indeed, cultured astrocytes responded to proteasomal inhibition by preventing the reduction of c-K-Ras. A fraction of K-Ras protein accumulated in the presence of ROS and cycloheximide, while a substantial proportion was continuously synthesized. These data indicate that ROS regulate in a complementary fashion p21^Ras isoforms in primary astrocytes: K-Ras is rapidly and transiently induced by post-translational and post-transcriptional mechanisms, while H-Ras is stably induced by mRNA accumulation. We suggest that K-Ras and H-Ras are ROS sensors that adapt cells to metabolic needs and oxidative stress. Full article

(This article belongs to the Special Issue Astrocyte Antioxidant Systems)

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Open AccessArticle

Deletion of TXNIP Mitigates High-Fat Diet-Impaired Angiogenesis and Prevents Inflammation in a Mouse Model of Critical Limb Ischemia

by Sally L. Elshaer, Islam N. Mohamed, Maha Coucha, Sara Altantawi, Wael Eldahshan, Megan L. Bartasi, Ahmed Y. Shanab, Renee Lorys and Azza B. El-Remessy

Antioxidants 2017, 6(3), 47; https://doi.org/10.3390/antiox6030047 - 29 Jun 2017

Cited by 28 | Viewed by 7618

Abstract

Background: Previous work demonstrated that high-fat diet (HFD) triggered thioredoxin-interacting protein (TXNIP) and that silencing TXNIP prevents diabetes-impaired vascular recovery. Here, we examine the impact of genetic deletion of TXNIP on HFD-impaired vascular recovery using hind limb ischemia model. Methods: Wild type mice [...] Read more.

Background: Previous work demonstrated that high-fat diet (HFD) triggered thioredoxin-interacting protein (TXNIP) and that silencing TXNIP prevents diabetes-impaired vascular recovery. Here, we examine the impact of genetic deletion of TXNIP on HFD-impaired vascular recovery using hind limb ischemia model. Methods: Wild type mice (WT, C57Bl/6) and TXNIP knockout mice (TKO) were fed either normal chow diet (WT-ND and TKO-ND) or 60% high-fat diet (WT-HFD and TKO-HFD). After four weeks of HFD, unilateral hind limb ischemia was performed and blood flow was measured using Laser doppler scanner at baseline and then weekly for an additional three weeks. Vascular density, nitrative stress, infiltration of CD68+ macrophages, and expression of inflammasome, vascular endothelial growth factor (VEGF), VEGF receptor-2 were examined by slot blot, Western blot and immunohistochemistry. Results: By week 8, HFD caused similar increases in weight, cholesterol and triglycerides in both WT and TKO. At week 4 and week 8, HFD significantly impaired glucose tolerance in WT and to a lesser extent in TKO. HFD significantly impaired blood flow and vascular density (CD31 labeled) in skeletal muscle of WT mice compared to ND but not in TKO. HFD and ischemia significantly induced tyrosine nitration, and systemic IL-1β and infiltration of CD68+ cells in skeletal muscle from WT but not from TKO. HFD significantly increased cleaved-caspase-1 and IL-1 β compared to ND. Under both ND, ischemia tended to increase VEGF expression and increased VEGFR2 activation in WT only but not TKO. Conclusion: Similar to prior observation in diabetes, HFD-induced obesity can compromise vascular recovery in response to ischemic insult. The mechanism involves increased TXNIP-NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome activation, nitrative stress and impaired VEGFR2 activation. Deletion of TXNIP restored blood flow, reduced nitrative stress and blunted inflammasome-mediated inflammation; however, it did not impact VEGF/VEGFR2 in HFD. Targeting TXNIP-NLRP3 inflammasome can provide potential therapeutic target in obesity-induced vascular complication. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

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Open AccessArticle

Evaluating Modern Techniques for the Extraction and Characterisation of Sunflower (Hellianthus annus L.) Seeds Phenolics

by Panagiotis Zoumpoulakis, Vassilia J. Sinanoglou, Eleni Siapi, George Heropoulos and Charalampos Proestos

Antioxidants 2017, 6(3), 46; https://doi.org/10.3390/antiox6030046 - 24 Jun 2017

Cited by 25 | Viewed by 7338

Abstract

Recently there is a great interest in using high energy techniques (HET) which involve microwave or ultrasound-assisted extraction (MAE and UAE) for isolation of natural bioactive compounds from plant foods. Such bioactive compounds are phenolics which were determined from sunflower (Helianthus annuus [...] Read more.

Recently there is a great interest in using high energy techniques (HET) which involve microwave or ultrasound-assisted extraction (MAE and UAE) for isolation of natural bioactive compounds from plant foods. Such bioactive compounds are phenolics which were determined from sunflower (Helianthus annuus L.) kernels and hulls (defatted) utilising two different high energy extraction techniques, ultrasound and microwave assisted solvent extraction. All samples were characterised by ultra-high-performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MS). The effect of parameters such as the nature of the solvent, volume of solvent, temperature and time is discussed. It is proved that the techniques applied had reduced solvent consumption and shorter extraction times, and extraction yields of the analytes were equal to or to some extent higher than those obtained with conventional techniques. Total Phenolic Composition (TPC) of samples examined was studied by the Folin-Ciocalteu method and results were presented in μg gallic acid equivalents (GAE)/g dry extract. Kernels proved to have the higher amount of TPC while the press residues had shown comparable TPC results. The antioxidant activity of samples was spectrophotometrically determined by 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay using Butylated hydroxyl toluene (BHT) as reference compound to compare with samples. Sunflower seeds (kernels) showed again the highest antiradical efficiency (AE) compared to hulls and press-residue extract. Afterwards, ferric reducing ability of plasma (FRAP) and trolox equivalent antioxidant capacity (TEAC) assays were used for measuring the antioxidant capacity of samples. Press residue, a by-product of sunflower oil extraction, contained phenolics as shown by UHPLC-ESI-MS analysis. Hence, later on these compounds can be possibly utilised by food or neutraceutical industries. Phenolic substances characterised in hulls, kernels, and press residue were phenolic acids, mainly chlorogenic, caffeic, cinnamic, 4-hydroxybenzoic and p-coumaric. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Health Promotion)

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Open AccessReview

Vitamin E and Alzheimer’s Disease—Is It Time for Personalized Medicine?

by Breana Cervantes and Lynn M. Ulatowski

Antioxidants 2017, 6(3), 45; https://doi.org/10.3390/antiox6030045 - 24 Jun 2017

Cited by 35 | Viewed by 7422

Abstract

For the last two decades, it has been hotly debated whether vitamin E—the major lipid-soluble antioxidant, which functions to maintain neurological integrity—is efficacious as a therapy for Alzheimer’s disease. Several factors key to the debate, include (1) which of the eight naturally-occurring vitamin [...] Read more.

For the last two decades, it has been hotly debated whether vitamin E—the major lipid-soluble antioxidant, which functions to maintain neurological integrity—is efficacious as a therapy for Alzheimer’s disease. Several factors key to the debate, include (1) which of the eight naturally-occurring vitamin E forms should be used; (2) how combination treatments affect vitamin E efficacy; and (3) safety concerns that most-recently resurfaced after the results of the Selenium and vitamin E Cancer prevention trial SELECT prostate cancer trial. However, with the advent of new genetic technologies and identifications of vitamin E-modulating single nucleotide polymorphisms (SNPs), we propose that clinical trials addressing the question “Is vitamin E an effective treatment for Alzheimer’s disease” should consider a more focused and personalized medicine approach to designing experiments. An individual’s naturally-occurring SNP variants may indeed influence vitamin E’s therapeutic effect on Alzheimer’s disease. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Health Promotion)

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