Open AccessArticle
In Vitro and In Vivo Antioxidant and Anti-Hyperglycemic Activities of Moroccan Oat Cultivars
Antioxidants 2017, 6(4), 102; doi:10.3390/antiox6040102 -
Abstract
Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible
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Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible mechanisms of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids were quantified in our samples including ferulic, p-hydroxybenzoic, caffeic, salicylic, syringic, sinapic, p-coumaric and chlorogenic acids. The Oat extract (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose (FBG) and oxidative stress markers, including Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by their inhibitory activities on α-amylase (723.91 μg/mL and 1027.14 μg/mL) and α-glucosidase (1548.12 μg/mL & 1803.52 μg/mL) enzymes by mean of a mixed inhibition. Full article
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Open AccessArticle
Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice
Antioxidants 2017, 6(4), 101; doi:10.3390/antiox6040101 -
Abstract
Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of
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Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex vivo, in adult male wild-type and dystrophin-deficient mdx mice, with and without a 14-day antioxidant intervention. The enzymatic activities of muscle citrate synthase, phosphofructokinase, and lactate dehydrogenase were assessed using spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction and altered biochemical status. Chronic tempol supplementation in the drinking water increased diaphragm functional capacity and citrate synthase and lactate dehydrogenase enzymatic activities, restoring all values to wild-type levels. Chronic supplementation with tempol recovers force-generating capacity and metabolic enzyme activity in mdx diaphragm. These findings may have relevance in the search for therapeutic strategies in neuromuscular disease. Full article
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Open AccessArticle
Effects of the Macular Carotenoid Lutein in Human Retinal Pigment Epithelial Cells
Antioxidants 2017, 6(4), 100; doi:10.3390/antiox6040100 -
Abstract
Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Oxidative stress-induced damage to the RPE occurs as part of the pathogenesis of age-related macular degeneration and neovascular retinopathies (e.g., retinopathy of prematurity, diabetic retinopathy). The xanthophyll carotenoids, lutein and zeaxanthin,
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Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Oxidative stress-induced damage to the RPE occurs as part of the pathogenesis of age-related macular degeneration and neovascular retinopathies (e.g., retinopathy of prematurity, diabetic retinopathy). The xanthophyll carotenoids, lutein and zeaxanthin, are selectively taken up by the RPE, preferentially accumulated in the human macula, and transferred to photoreceptors. These macular xanthophylls protect the macula (and the broader retina) via their antioxidant and photo-protective activities. This study was designed to investigate effects of various carotenoids (β-carotene, lycopene, and lutein) on RPE cells subjected to either hypoxia or oxidative stress, in order to determine if there is effect specificity for macular pigment carotenoids. Using human RPE-derived ARPE-19 cells as an in vitro model, we exposed RPE cells to various concentrations of the specific carotenoids, followed by either graded hypoxia or oxidative stress using tert-butyl hydroperoxide (tBHP). The results indicate that lutein and lycopene, but not β-carotene, inhibit cell growth in undifferentiated ARPE-19 cells. Moreover, cell viability was decreased under hypoxic conditions. Pre-incubation of ARPE-19 cells with lutein or lycopene protected against tBHP-induced cell loss and cell co-exposure of lutein or lycopene with tBHP essentially neutralized tBHP-dependent cell death at tBHP concentrations up to 500 μM. Our findings indicate that lutein and lycopene inhibit the growth of human RPE cells and protect the RPE against oxidative stress-induced cell loss. These findings contribute to the understanding of the protective mechanisms attributable to retinal xanthophylls in eye health and retinopathies. Full article
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Open AccessReview
Recent Advances in our Understanding of Tocopherol Biosynthesis in Plants: An Overview of Key Genes, Functions, and Breeding of Vitamin E Improved Crops
Antioxidants 2017, 6(4), 99; doi:10.3390/antiox6040099 -
Abstract
Tocopherols, together with tocotrienols and plastochromanols belong to a group of lipophilic compounds also called tocochromanols or vitamin E. Considered to be one of the most powerful antioxidants, tocochromanols are solely synthesized by photosynthetic organisms including plants, algae, and cyanobacteria and, therefore, are
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Tocopherols, together with tocotrienols and plastochromanols belong to a group of lipophilic compounds also called tocochromanols or vitamin E. Considered to be one of the most powerful antioxidants, tocochromanols are solely synthesized by photosynthetic organisms including plants, algae, and cyanobacteria and, therefore, are an essential component in the human diet. Tocochromanols potent antioxidative properties are due to their ability to interact with polyunsaturated acyl groups and scavenge lipid peroxyl radicals and quench reactive oxygen species (ROS), thus protecting fatty acids from lipid peroxidation. In the plant model species Arabidopsis thaliana, the required genes for tocopherol biosynthesis and functional roles of tocopherols were elucidated in mutant and transgenic plants. Recent research efforts have led to new outcomes for the vitamin E biosynthetic and related pathways, and new possible alternatives for the biofortification of important crops have been suggested. Here, we review 30 years of research on tocopherols in model and crop species, with emphasis on the improvement of vitamin E content using transgenic approaches and classical breeding. We will discuss future prospects to further improve the nutritional value of our food. Full article
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Open AccessArticle
Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage
Antioxidants 2017, 6(4), 98; doi:10.3390/antiox6040098 -
Abstract
Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress
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Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios. Full article
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Open AccessArticle
The Subcellular Distribution of Alpha-Tocopherol in the Adult Primate Brain and Its Relationship with Membrane Arachidonic Acid and Its Oxidation Products
Antioxidants 2017, 6(4), 97; doi:10.3390/antiox6040097 -
Abstract
The relationship between α-tocopherol, a known antioxidant, and polyunsaturated fatty acid (PUFA) oxidation, has not been directly investigated in the primate brain. This study characterized the membrane distribution of α-tocopherol in brain regions and investigated the association between membrane α-tocopherol and PUFA content,
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The relationship between α-tocopherol, a known antioxidant, and polyunsaturated fatty acid (PUFA) oxidation, has not been directly investigated in the primate brain. This study characterized the membrane distribution of α-tocopherol in brain regions and investigated the association between membrane α-tocopherol and PUFA content, as well as brain PUFA oxidation products. Nuclear, myelin, mitochondrial, and neuronal membranes were isolated using a density gradient from the prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC) of adult rhesus monkeys (n = 9), fed a stock diet containing vitamin E (α-, γ-tocopherol intake: ~0.7 µmol/kg body weight/day, ~5 µmol/kg body weight/day, respectively). α-tocopherol, PUFAs, and PUFA oxidation products were measured using high performance liquid chromatography (HPLC), gas chromatography (GC) and liquid chromatography-gas chromatography/mass spectrometry (LC-GC/MS) respectively. α-Tocopherol (ng/mg protein) was highest in nuclear membranes (p < 0.05) for all regions except HC. In PFC and ST, arachidonic acid (AA, µg/mg protein) had a similar membrane distribution to α-tocopherol. Total α-tocopherol concentrations were inversely associated with AA oxidation products (isoprostanes) (p < 0.05), but not docosahexaenoic acid oxidation products (neuroprostanes). This study reports novel data on α-tocopherol accumulation in primate brain regions and membranes and provides evidence that α-tocopherol and AA are similarly distributed in PFC and ST membranes, which may reflect a protective effect of α-tocopherol against AA oxidation. Full article
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Open AccessReview
Carotenoids from Marine Organisms: Biological Functions and Industrial Applications
Antioxidants 2017, 6(4), 96; doi:10.3390/antiox6040096 -
Abstract
As is the case for terrestrial organisms, carotenoids represent the most common group of pigments in marine environments. They are generally biosynthesized by all autotrophic marine organisms, such as bacteria and archaea, algae and fungi. Some heterotrophic organisms also contain carotenoids probably accumulated
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As is the case for terrestrial organisms, carotenoids represent the most common group of pigments in marine environments. They are generally biosynthesized by all autotrophic marine organisms, such as bacteria and archaea, algae and fungi. Some heterotrophic organisms also contain carotenoids probably accumulated from food or partly modified through metabolic reactions. These natural pigments are divided into two chemical classes: carotenes (such as lycopene and α- and β-carotene) that are composed of hydrogen and carbon; xanthophylls (such as astaxanthin, fucoxanthin and lutein), which are constituted by hydrogen, carbon and oxygen. Carotenoids, as antioxidant compounds, assume a key role in the protection of cells. In fact, quenching of singlet oxygen, light capture and photosynthesis protection are the most relevant biological functions of carotenoids. The present review aims at describing (i) the biological functions of carotenoids and their benefits for human health, (ii) the most common carotenoids from marine organisms and (iii) carotenoids having large success in pharmaceutical, nutraceutical and cosmeceutical industries, highlighting the scientific progress in marine species cultivation for natural pigments production. Full article
Open AccessReview
Vitamin E Bioavailability: Mechanisms of Intestinal Absorption in the Spotlight
Antioxidants 2017, 6(4), 95; doi:10.3390/antiox6040095 -
Abstract
Vitamin E is an essential fat-soluble micronutrient whose effects on human health can be attributed to both antioxidant and non-antioxidant properties. A growing number of studies aim to promote vitamin E bioavailability in foods. It is thus of major interest to gain deeper
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Vitamin E is an essential fat-soluble micronutrient whose effects on human health can be attributed to both antioxidant and non-antioxidant properties. A growing number of studies aim to promote vitamin E bioavailability in foods. It is thus of major interest to gain deeper insight into the mechanisms of vitamin E absorption, which remain only partly understood. It was long assumed that vitamin E was absorbed by passive diffusion, but recent data has shown that this process is actually far more complex than previously thought. This review describes the fate of vitamin E in the human gastrointestinal lumen during digestion and focuses on the proteins involved in the intestinal membrane and cellular transport of vitamin E across the enterocyte. Special attention is also given to the factors modulating both vitamin E micellarization and absorption. Although these latest results significantly improve our understanding of vitamin E intestinal absorption, further studies are still needed to decipher the molecular mechanisms driving this multifaceted process. Full article
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Open AccessMeeting Report
Symposium on Vitamin C, 15th September 2017; Part of the Linus Pauling Institute’s 9th International Conference on Diet and Optimum Health
Antioxidants 2017, 6(4), 94; doi:10.3390/antiox6040094 -
Abstract
The Linus Pauling Institute’s 9th International Conference on Diet and Optimum Health took place on 13–15 September 2017 in Corvallis, OR, USA, on the beautiful Oregon State University campus [...]
Full article
Open AccessReview
Tocotrienols: A Family of Molecules with Specific Biological Activities
Antioxidants 2017, 6(4), 93; doi:10.3390/antiox6040093 -
Abstract
Vitamin E is a generic term frequently used to group together eight different molecules, namely: α-, β-, γ- and δ-tocopherol and the corresponding tocotrienols. The term tocopherol and eventually Vitamin E and its related activity was originally based on the capacity of countering
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Vitamin E is a generic term frequently used to group together eight different molecules, namely: α-, β-, γ- and δ-tocopherol and the corresponding tocotrienols. The term tocopherol and eventually Vitamin E and its related activity was originally based on the capacity of countering foetal re-absorption in deficient rodents or the development of encephalomalacia in chickens. In humans, Vitamin E activity is generally considered to be solely related to the antioxidant properties of the tocolic chemical structure. In recent years, several reports have shown that specific activities exist for each different tocotrienol form. In this short review, tocotrienol ability to inhibit cancer cell growth and induce apoptosis thanks to specific mechanisms, not shared by tocopherols, such as the binding to Estrogen Receptor-β (ERβ) and the triggering of endoplasmic reticulum (EndoR) stress will be described. The neuroprotective activity will also be presented and discussed. We propose that available studies strongly indicate that specific forms of tocotrienols have a distinct mechanism and biological activity, significantly different from tocopherol and more specifically from α-tocopherol. We therefore suggest not pooling them together within the broad term “Vitamin E” on solely the basis of their putative antioxidant properties. This option implies obvious consequences in the assessment of dietary Vitamin E adequacy and, probably more importantly, on the possibility of evaluating a separate biological variable, determinant in the relationship between diet and health. Full article
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Open AccessArticle
MnSOD and Cyclin B1 Coordinate a Mito-Checkpoint during Cell Cycle Response to Oxidative Stress
Antioxidants 2017, 6(4), 92; doi:10.3390/antiox6040092 -
Abstract
Communication between the nucleus and mitochondrion could coordinate many cellular processes. While the mechanisms regulating this communication are not completely understood, we hypothesize that cell cycle checkpoint proteins coordinate the cross-talk between nuclear and mitochondrial functions following oxidative stress. Human normal skin fibroblasts,
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Communication between the nucleus and mitochondrion could coordinate many cellular processes. While the mechanisms regulating this communication are not completely understood, we hypothesize that cell cycle checkpoint proteins coordinate the cross-talk between nuclear and mitochondrial functions following oxidative stress. Human normal skin fibroblasts, representative of the G2-phase, were irradiated with 6 Gy of ionizing radiation and assayed for cyclin B1 translocation, mitochondrial function, reactive oxygen species (ROS) levels, and cytotoxicity. In un-irradiated controls, cyclin B1 was found primarily in the nucleus of G2-cells. However, following irradiation, cyclin B1 was excluded from the nucleus and translocated to the cytoplasm and mitochondria. These observations were confirmed further by performing transmission electron microscopy and cell fractionation assays. Cyclin B1 was absent in mitochondria isolated from un-irradiated G2-cells and present in irradiated G2-cells. Radiation-induced translocation of cyclin B1 from the nucleus to the mitochondrion preceded changes in the activities of mitochondrial proteins, that included decreases in the activities of aconitase and the mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD), and increases in complex II activity. Changes in the activities of mito-proteins were followed by an increase in dihydroethidium (DHE) oxidation (indicative of increased superoxide levels) and loss of the mitochondrial membrane potential, events that preceded the restart of the stalled cell cycle and subsequently the loss in cell viability. Comparable results were also observed in un-irradiated control cells overexpressing mitochondria-targeted cyclin B1. These results indicate that MnSOD and cyclin B1 coordinate a cross-talk between nuclear and mitochondrial functions, to regulate a mito-checkpoint during the cell cycle response to oxidative stress. Full article
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Open AccessReview
Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease
Antioxidants 2017, 6(4), 91; doi:10.3390/antiox6040091 -
Abstract
Moringa Oleifera (MO), a plant from the family Moringacea is a major crop in Asia and Africa. MO has been studied for its health properties, attributed to the numerous bioactive components, including vitamins, phenolic acids, flavonoids, isothiocyanates, tannins and saponins, which
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Moringa Oleifera (MO), a plant from the family Moringacea is a major crop in Asia and Africa. MO has been studied for its health properties, attributed to the numerous bioactive components, including vitamins, phenolic acids, flavonoids, isothiocyanates, tannins and saponins, which are present in significant amounts in various components of the plant. Moringa Oleifera leaves are the most widely studied and they have shown to be beneficial in several chronic conditions, including hypercholesterolemia, high blood pressure, diabetes, insulin resistance, non-alcoholic liver disease, cancer and overall inflammation. In this review, we present information on the beneficial results that have been reported on the prevention and alleviation of these chronic conditions in various animal models and in cell studies. The existing limited information on human studies and Moringa Oleifera leaves is also presented. Overall, it has been well documented that Moringa Oleifera leaves are a good strategic for various conditions associated with heart disease, diabetes, cancer and fatty liver. Full article
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Open AccessReview
Nox, Reactive Oxygen Species and Regulation of Vascular Cell Fate
Antioxidants 2017, 6(4), 90; doi:10.3390/antiox6040090 -
Abstract
The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell
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The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell fate. The major source of ROS generated within the vascular system is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (Nox), of which seven members have been characterized. The Nox family are critical determinants of the redox state within the vessel wall that dictate, in part the pathophysiology of several vascular phenotypes. This review highlights the putative role of ROS in controlling vascular fate by promoting endothelial dysfunction, altering vascular smooth muscle phenotype and dictating resident vascular stem cell fate, all of which contribute to intimal medial thickening and vascular disease progression. Full article
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Open AccessArticle
Trans-Plasma Membrane Electron Transport and Ascorbate Efflux by Skeletal Muscle
Antioxidants 2017, 6(4), 89; doi:10.3390/antiox6040089 -
Abstract
Trans-plasma membrane electron transport (tPMET) and the antioxidant roles of ascorbate reportedly play a role in protection of cells from damage by reactive oxygen species, which have been implicated in causing metabolic dysfunction such as insulin resistance. Skeletal muscle comprises the largest whole-body
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Trans-plasma membrane electron transport (tPMET) and the antioxidant roles of ascorbate reportedly play a role in protection of cells from damage by reactive oxygen species, which have been implicated in causing metabolic dysfunction such as insulin resistance. Skeletal muscle comprises the largest whole-body organ fraction suggesting a potential role of tPMET and ascorbate export as a major source of extracellular antioxidant. We hypothesized that skeletal muscle is capable of tPMET and ascorbate efflux. To measure these processes, we assayed the ability of cultured muscle cells, satellite cells, and isolated extensor digitorum longus (EDL) and soleus (SOL) to reduce two extracellular electron acceptors, water soluble tetrazolium salt 1 (WST-1), and dichlorophenolindophenol (DPIP). Ascorbate oxidase (AO) was utilized to determine which portion of WST-1 reduction was dependent on ascorbate efflux. We found that muscle cells can reduce extracellular electron acceptors. In C2C12 myotubes and satellite cells, a substantial portion of this reduction was dependent on ascorbate. In myotubes, glucose transporter 1 (GLUT1) inhibitors along with a pan-GLUT inhibitor suppressed tPMET and ascorbate efflux, while a GLUT4 inhibitor had no effect. The adenosine 5′-monophosphate (AMP)-activated protein kinase activator 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) suppressed both tPMET and ascorbate efflux by myotubes, while insulin had no effect. Taken together, our data suggest that muscle cells are capable of tPMET and ascorbate efflux supported by GLUT1, thus illustrating a model in which resting muscle exports electrons and antioxidant to the extracellular environment. Full article
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Open AccessReview
Polyphenols as Promising Drugs against Main Breast Cancer Signatures
Antioxidants 2017, 6(4), 88; doi:10.3390/antiox6040088 -
Abstract
Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as
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Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs) and epidermal growth factor receptor 2 (HER2). Tumors with none of these receptors are classified as triple negative breast cancer (TNBC) and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation. Full article
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Open AccessArticle
The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues
Antioxidants 2017, 6(4), 87; doi:10.3390/antiox6040087 -
Abstract
Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition
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Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure. Specifically, at two months post-radiation, MnTE-2-PyP inhibited the number of α-smooth muscle actin positive fibroblasts induced by radiation and at six months post-radiation, MnTE-2-PyP significantly reduced collagen deposition (fibrosis) in the skin and bladder tissues of irradiated mice. Radiation also resulted in changes to T cells. At two months post-radiation, there was a reduction of Th1-producing splenocytes, which resulted in reduced Th1:Th2 ratios. MnTE-2-PyP maintained Th1:Th2 ratios similar to unirradiated mice. At six months post-radiation, increased T cells were observed in the adipose tissues. MnTE-2-PyP treatment inhibited this increase. Thus, MnTE-2-PyP treatment maintains normal fibroblast function and T cell immunity months after radiation exposure. We believe that one of the reasons MnTE-2-PyP is a potent radioprotector is due to its protection of multiple cell types from radiation damage. Full article
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Open AccessReview
Insights into the Dichotomous Regulation of SOD2 in Cancer
Antioxidants 2017, 6(4), 86; doi:10.3390/antiox6040086 -
Abstract
While loss of antioxidant expression and the resultant oxidant-dependent damage to cellular macromolecules is key to tumorigenesis, it has become evident that effective oxidant scavenging is conversely necessary for successful metastatic spread. This dichotomous role of antioxidant enzymes in cancer highlights their context-dependent
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While loss of antioxidant expression and the resultant oxidant-dependent damage to cellular macromolecules is key to tumorigenesis, it has become evident that effective oxidant scavenging is conversely necessary for successful metastatic spread. This dichotomous role of antioxidant enzymes in cancer highlights their context-dependent regulation during different stages of tumor development. A prominent example of an antioxidant enzyme with such a dichotomous role and regulation is the mitochondria-localized manganese superoxide dismutase SOD2 (MnSOD). SOD2 has both tumor suppressive and promoting functions, which are primarily related to its role as a mitochondrial superoxide scavenger and H2O2 regulator. However, unlike true tumor suppressor- or onco-genes, the SOD2 gene is not frequently lost, or rarely mutated or amplified in cancer. This allows SOD2 to be either repressed or activated contingent on context-dependent stimuli, leading to its dichotomous function in cancer. Here, we describe some of the mechanisms that underlie SOD2 regulation in tumor cells. While much is known about the transcriptional regulation of the SOD2 gene, including downregulation by epigenetics and activation by stress response transcription factors, further research is required to understand the post-translational modifications that regulate SOD2 activity in cancer cells. Moreover, future work examining the spatio-temporal nature of SOD2 regulation in the context of changing tumor microenvironments is necessary to allows us to better design oxidant- or antioxidant-based therapeutic strategies that target the adaptable antioxidant repertoire of tumor cells. Full article
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Open AccessArticle
Treatment with a Catalytic Superoxide Dismutase (SOD) Mimetic Improves Liver Steatosis, Insulin Sensitivity, and Inflammation in Obesity-Induced Type 2 Diabetes
Antioxidants 2017, 6(4), 85; doi:10.3390/antiox6040085 -
Abstract
Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition and a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired insulin signaling leads to hyperglycemia and long-term complications, including metabolic liver dysfunction, resulting in non-alcoholic fatty liver disease (NAFLD).
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Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition and a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired insulin signaling leads to hyperglycemia and long-term complications, including metabolic liver dysfunction, resulting in non-alcoholic fatty liver disease (NAFLD). The manganese metalloporphyrin superoxide dismustase (SOD) mimetic, manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnP), is an oxidoreductase known to scavenge reactive oxygen species (ROS) and decrease pro-inflammatory cytokine production, by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. We hypothesized that targeting oxidative stress-induced inflammation with MnP would assuage liver complications and enhance insulin sensitivity and glucose tolerance in a high-fat diet (HFD)-induced mouse model of T2D. During 12 weeks of feeding, we saw significant improvements in weight, hepatic steatosis, and biomarkers of liver dysfunction with redox modulation by MnP treatment in HFD-fed mice. Additionally, MnP treatment improved insulin sensitivity and glucose tolerance, while reducing serum insulin and leptin levels. We attribute these effects to redox modulation and inhibition of hepatic NF-κB activation, resulting in diminished ROS and pro-inflammatory cytokine production. This study highlights the importance of controlling oxidative stress and secondary inflammation in obesity-mediated insulin resistance and T2D. Our data confirm the role of NF-κB-mediated inflammation in the development of T2D, and demonstrate the efficacy of MnP in preventing the progression to disease by specifically improving liver pathology and hepatic insulin resistance in obesity. Full article
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Open AccessReview
Effects of Cocoa Antioxidants in Type 2 Diabetes Mellitus
Antioxidants 2017, 6(4), 84; doi:10.3390/antiox6040084 -
Abstract
Type 2 Diabetes mellitus (T2D) is the most common form of diabetes and one of the most common chronic diseases. Control of hyperglycaemia by hypoglycaemic drugs is insufficient in for patients and nutritional approaches are currently being explored. Natural dietary compounds such as
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Type 2 Diabetes mellitus (T2D) is the most common form of diabetes and one of the most common chronic diseases. Control of hyperglycaemia by hypoglycaemic drugs is insufficient in for patients and nutritional approaches are currently being explored. Natural dietary compounds such as flavonoids, abundant in fruits and vegetables, have received broad attention because of their potential capacity to act as anti-diabetic agents. Especially cocoa flavonoids have been proved to ameliorate important hallmarks of T2D. In this review, an update of the most relevant reports published during the last decade in cell culture, animal models and human studies is presented. Most results support an anti-diabetic effect of cocoa flavonoids by enhancing insulin secretion, improving insulin sensitivity in peripheral tissues, exerting a lipid-lowering effect and preventing the oxidative and inflammatory damages associated to the disease. While it could be suggested that daily consumption of flavanols from cocoa or dark chocolate would constitute a potential preventive tool useful for the nutritional management of T2D, this recommendation should be cautious since most of commercially available soluble cocoa products or chocolates contain low amount of flavanols and are rich in sugar and calories that may aggravate glycaemic control in T2D patients. Full article
Open AccessArticle
Selenium Concentrations for Maximisation of Thioredoxin Reductase 2 Activity and Upregulation of Its Gene Transcripts in Senescent Human Fibroblasts
Antioxidants 2017, 6(4), 83; doi:10.3390/antiox6040083 -
Abstract
Thioredoxin reductase 2 (TR2) activity, its gene transcripts, and hydrogen peroxide (H2O2) generation were examined in biochemically identified early-senescent P20 and senescent P30 fibroblasts subcultured in media (MEM2–MEM8) containing Se concentrations at 1.25, 2.5, 3.5, 5.0, 6.0, 7.0, and
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Thioredoxin reductase 2 (TR2) activity, its gene transcripts, and hydrogen peroxide (H2O2) generation were examined in biochemically identified early-senescent P20 and senescent P30 fibroblasts subcultured in media (MEM2–MEM8) containing Se concentrations at 1.25, 2.5, 3.5, 5.0, 6.0, 7.0, and 8.0 µM, respectively. Although TR2 activity was moderately increased in P20 and P30 cells subcultured in routine growth medium (MEM1), there were progressive significant activity increases in the same cells subcultured in MEM2–MEM8. Such increases were proportional to Se concentration and peaked in P30 cells incubated with MEM7 and MEM8. H2O2 generation underwent progressiveincreases in MEM1-incubated P20 and P30 cells, peaking in the latter, but was gradually lowered in those incubated with MEM2–MEM8, reaching its lowest values when cells were incubated with MEM7 and MEM8. In parallel, TR2 gene transcripts underwent significant upregulation in P20 cells and higher magnitude upregulation in P30 cells subcultured in MEM2, MEM4, and MEM8 compared to those recorded for P5 pre-senescent cells subcultured in the same media. The computed Km Se values with respect to TR2 activity equaled 3.34 and 4.98 µM for P20 and P30 cells, respectively, with corresponding Vmax activities of 55.9 and 96.2 nmol/min/mg protein. It is concluded that senescent P30 cells utilize more Se and achieve maximal TR2 activity to combat oxidative injury. Full article
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