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1.
Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions.
Liakopoulos, V, Roumeliotis, S, Zarogiannis, S, Eleftheriadis, T, Mertens, PR
Seminars in dialysis. 2019;(1):58-71
Abstract
Oxidative stress (OS) is the result of prooxidant molecules overwhelming the antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated inflammation and OS, due to loss of antioxidants during dialysis and activation of white blood cells triggering production of reactive oxygen species. Dialysis vintage, dialysis methods, and type and condition of vascular access, biocompatibility of dialyzer membrane and dialysate, iron administration, and anemia all can play a role in aggravating OS, which in turn has been associated with increased morbidity and mortality. Oral or intravenous administration of antioxidants may detoxify the oxidative molecules and at least in part repair OS-mediated tissue damage. Lifestyle interventions and optimization of a highly biocompatible HD procedure might ameliorate OS development in dialysis.
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2.
The Role of Oxidative Stress, Adhesion Molecules and Antioxidants in Preeclampsia.
Haram, K, Mortensen, JH, Myking, O, Magann, EF, Morrison, JC
Current hypertension reviews. 2019;(2):105-112
Abstract
Oxidative stress is a consequence of reduction in the antioxidant capacity and excessive production of reactive oxygen and nitrogen species (ROS). Oxidative agents, which are overproduced due to ischemic-reperfusion injury in the placenta, may overwhelm the normal antioxidant activity. This imbalance is a key feature in the pathogenesis of preeclampsia. A decrease in glutathione peroxidase (GPX) activity is associated with the synthesis of vasoconstrictive eicosanoids such as F2-isoprostanes and thromboxane, which are known to be upregulated in preeclampsia. Biochemical markers of lipid peroxidation, such as malondialdehyde and F2-isoprostane in the placenta, are also increased. Adhesion molecules participate in the pathophysiology of preeclampsia by contributing to a reduced invasion by the trophoblast and increased vascular endothelial damage. Superoxide dismutase (SOD), catalase (CAT) and GPX play important roles counteracting oxidative stress. Other antioxidant factors participate in the etiology of preeclampsia. Levels of antioxidants such as Lycopene, Coenzyme 10, as well as some vitamins, are reduced in preeclamptic gestations.
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3.
Dietary phytochemicals with anti-oxidant and pro-oxidant activities: A double-edged sword in relation to adjuvant chemotherapy and radiotherapy?
Fernando, W, Rupasinghe, HPV, Hoskin, DW
Cancer letters. 2019;:168-177
Abstract
Many advances have been made in the development and introduction of new anti-cancer drugs to the clinic. However, limited attention has been paid to improving the efficacy of currently available treatments through complementary phytochemical interventions that affect cellular reactive oxygen species (ROS) levels, which are important for the etiology of certain cancers and the effectiveness of radiotherapy and some chemotherapy. In this regard, the maintenance of redox homeostasis may be influenced by the intake of anti-oxidant and pro-oxidant compounds from dietary sources. Interestingly, certain dietary phytochemicals exhibit both anti-oxidant and pro-oxidant activities, depending on their concentration and cellular microenvironment. There is evidence that concurrent administration of some dietary phytochemicals enhances the efficacy of certain cancer treatments by increasing intracellular ROS accumulation. Paradoxically, consumption of the same dietary phytochemicals under conditions that result in the scavenging of ROS might also negatively affect the outcome of ROS-dependent cancer treatments. This review discusses the potential impact of consuming dietary phytochemicals with anti-oxidant and/or pro-oxidant activities on the effectiveness of concurrent chemotherapy and/or radiotherapy in cancer patients.
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4.
Reactive oxygen species as mediators of oxygen signaling during fetal-to-neonatal circulatory transition.
Villamor, E, Moreno, L, Mohammed, R, Pérez-Vizcaíno, F, Cogolludo, A
Free radical biology & medicine. 2019;:82-96
Abstract
Reactive oxygen species (ROS) are frequently seen as pathological agents of oxidative stress. However, ROS are not always deleterious and can also act as cell signaling molecules. Vascular oxygen sensing and signaling during fetal-to-neonatal circulatory transition is a remarkable example of the physiological regulatory actions of ROS. The fetal relative hypoxic environment induces hypoxic pulmonary vasoconstriction (HPV) and ductus arteriosus (DA) relaxation favoring the presence of high pulmonary vascular resistance and right-to-left ductal shunt. At birth, the increase in oxygen tension causes relaxation of pulmonary arteries (PAs) and normoxic DA vasoconstriction (NDAV), thus diverting blood flow to the lungs. Although the response to changes in oxygen tension is diametrically opposite, the mechanisms responsible for HPV and NDAV appear to be the result of a similar interaction between triggering and modulating factors that lead to an increase in cytosolic Ca2+ concentration and Ca2+ sensitization of the contractile apparatus. Growing evidence points to an increase in ROS (mitochondria- and/or NADPH-derived superoxide and/or H2O2), leading to inhibition of voltage-gated K+ channels, membrane depolarization, and activation of voltage-gated L-type Ca2+ channels as critical events in the signaling pathway of both HPV and NDAV. Several groups of investigators have completed this pathway adding other elements such as neutral sphingomyelinase-derived ceramide, the sarcoplasmic/endoplasmic reticulum (through ryanodine and inositol 1,4,5-trisphosphate receptors), Rho kinase-mediated Ca2+ sensitization, or transient receptor potential channels. The present review focus on the role of ROS as mediators of the homeostatic oxygen sensing system during fetal and neonatal life not only in the PAs and DA but also in systemic arteries.
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5.
Reaction-Based Fluorescent Probes for the Detection and Imaging of Reactive Oxygen, Nitrogen, and Sulfur Species.
Wu, L, Sedgwick, AC, Sun, X, Bull, SD, He, XP, James, TD
Accounts of chemical research. 2019;(9):2582-2597
Abstract
This Account describes a range of strategies for the development of fluorescent probes for detecting reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive (redox-active) sulfur species (RSS). Many ROS/RNS have been implicated in pathological processes such as Alzheimer's disease, cancer, diabetes mellitus, cardiovascular disease, and aging, while many RSS play important roles in maintaining redox homeostasis, serving as antioxidants and acting as free radical scavengers. Fluorescence-based systems have emerged as one of the best ways to monitor the concentrations and locations of these often very short lived species. Because of the high levels of sensitivity and in particular their ability to be used for temporal and spatial sampling for in vivo imaging applications. As a direct result, there has been a huge surge in the development of fluorescent probes for sensitive and selective detection of ROS, RNS, and RSS within cellular environments. However, cellular environments are extremely complex, often with more than one species involved in a given biochemical process. As a result, there has been a rise in the development of dual-responsive fluorescent probes (AND-logic probes) that can monitor the presence of more than one species in a biological environment. Our aim with this Account is to introduce the fluorescent probes that we have developed for in vitro and in vivo measurement of ROS, RNS, and RSS. Fluorescence-based sensing mechanisms used in the construction of the probes include photoinduced electron transfer, intramolecular charge transfer, excited-state intramolecular proton transfer (ESIPT), and fluorescence resonance energy transfer. In particular, probes for hydrogen peroxide, hypochlorous acid, superoxide, peroxynitrite, glutathione, cysteine, homocysteine, and hydrogen sulfide are discussed. In addition, we describe the development of AND-logic-based systems capable of detecting two species, such as peroxynitrite and glutathione. One of the most interesting advances contained in this Account is our extension of indicator displacement assays (IDAs) to reaction-based indicator displacement assays (RIAs). In an IDA system, an indicator is allowed to bind reversibly to a receptor. Then a competitive analyte is introduced into the system, resulting in displacement of the indicator from the host, which in turn modulates the optical signal. With an RIA-based system, the indicator is cleaved from a preformed receptor-indicator complex rather than being displaced by the analyte. Nevertheless, without a doubt the most significant result contained in this Account is the use of an ESIPT-based probe for the simultaneous sensing of fibrous proteins/peptides AND environmental ROS/RNS.
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6.
Crosstalk between Calcium and ROS in Pathophysiological Conditions.
Feno, S, Butera, G, Vecellio Reane, D, Rizzuto, R, Raffaello, A
Oxidative medicine and cellular longevity. 2019;:9324018
Abstract
Calcium ions are highly versatile intracellular signals that regulate many cellular processes. The key to achieving this pleiotropic role is the spatiotemporal control of calcium concentration evoked by an extensive molecular repertoire of signalling components. Among these, reactive oxygen species (ROS) signalling, together with calcium signalling, plays a crucial role in controlling several physiopathological events. Although initially considered detrimental by-products of aerobic metabolism, it is now widely accepted that ROS, in subtoxic levels, act as signalling molecules. However, dysfunctions in the mechanisms controlling the physiological ROS concentration affect cellular homeostasis, leading to the pathogenesis of various disorders.
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7.
NEET Proteins: A New Link Between Iron Metabolism, Reactive Oxygen Species, and Cancer.
Mittler, R, Darash-Yahana, M, Sohn, YS, Bai, F, Song, L, Cabantchik, IZ, Jennings, PA, Onuchic, JN, Nechushtai, R
Antioxidants & redox signaling. 2019;(8):1083-1095
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Abstract
SIGNIFICANCE Cancer cells accumulate high levels of iron and reactive oxygen species (ROS) to promote their high metabolic activity and proliferation rate. However, high levels of iron and ROS can also lead to enhanced oxidative stress and the activation of cell death pathways such as apoptosis and ferroptosis. This has led to the proposal that different drugs that target iron and/or ROS metabolism could be used as anticancer drugs. However, due to the complex role iron and ROS play in cells, the majority of these drugs yielded mixed results, highlighting a critical need to identify new players in the regulation of iron and ROS homeostasis in cancer cells. Recent Advances: NEET proteins belong to a newly discovered class of iron-sulfur proteins (2Fe-2S) required for the regulation of iron and ROS homeostasis in cells. Recent studies revealed that the NEET proteins NAF-1 (CISD2) and mitoNEET (CISD1) play a critical role in promoting the proliferation of cancer cells, supporting tumor growth and metastasis. Moreover, the function of NEET proteins in cancer cells was found to be dependent of the degree of lability of their 2Fe-2S clusters. CRITICAL ISSUES NEET proteins could represent a key regulatory link between the maintenance of high iron and ROS in cancer cells, the activation of cell death and survival pathways, and cellular proliferation. FUTURE DIRECTIONS Because the function of NEET proteins depends on the lability of their clusters, drugs that target the 2Fe2S clusters of NEET proteins could be used as promising anticancer drugs.
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8.
The signalling role of ROS in the regulation of seed germination and dormancy.
Bailly, C
The Biochemical journal. 2019;(20):3019-3032
Abstract
Reactive oxygen species (ROS) are versatile compounds which can have toxic or signalling effects in a wide range living organisms, including seeds. They have been reported to play a pivotal role in the regulation of seed germination and dormancy but their mechanisms of action are still far from being fully understood. In this review, we sum-up the major findings that have been carried out this last decade in this field of research and which altogether shed a new light on the signalling roles of ROS in seed physiology. ROS participate in dormancy release during seed dry storage through the direct oxidation of a subset of biomolecules. During seed imbibition, the controlled generation of ROS is involved in the perception and transduction of environmental conditions that control germination. When these conditions are permissive for germination, ROS levels are maintained at a level which triggers cellular events associated with germination, such as hormone signalling. Here we propose that the spatiotemporal regulation of ROS production acts in concert with hormone signalling to regulate the cellular events involved in cell expansion associated with germination.
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9.
Iron and iron-dependent reactive oxygen species in the regulation of macrophages and fibroblasts in non-healing chronic wounds.
Wlaschek, M, Singh, K, Sindrilaru, A, Crisan, D, Scharffetter-Kochanek, K
Free radical biology & medicine. 2019;:262-275
Abstract
Chronic wounds pose a stern challenge to health care systems with growing incidence especially in the aged population. In the presence of increased iron concentrations, recruitment of monocytes from the circulation and activation towards ROS and RNS releasing M1 macrophages together with the persistence of senescent fibroblasts at the wound site are significantly enhanced. This unrestrained activation of pro-inflammatory macrophages and senescent fibroblasts has increasingly been acknowledged as main driver causing non-healing wounds. In a metaphor, macrophages act like stage directors of wound healing, resident fibroblasts constitute main actors and increased iron concentrations are decisive parts of the libretto, and - if dysregulated - are responsible for the development of non-healing wounds. This review will focus on recent cellular and molecular findings from chronic venous leg ulcers and diabetic non-healing wounds both constituting the most common pathologies often resulting in limb amputations of patients. This not only causes tremendous suffering and loss of life quality, but is also associated with an increase in mortality and a major socio-economic burden. Despite recent advances, the underlying molecular mechanisms are not completely understood. Overwhelming evidence shows that reactive oxygen species and the transition metal and trace element iron at pathological concentrations are crucially involved in a complex interplay between cells of different histogenetic origin and their extracellular niche environment. This interplay depends on a variety of cellular, non-cellular biochemical and cell biological mechanisms. Here, we will highlight recent progress in the field of iron-dependent regulation of macrophages and fibroblasts and related pathologies linked to non-healing chronic wounds.
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10.
In vitro and in vivo inhibition of maillard reaction products using amino acids, modified proteins, vitamins, and genistein: A review.
Mazumder, MAR, Hongsprabhas, P, Thottiam Vasudevan, R
Journal of food biochemistry. 2019;(12):e13089
Abstract
Maillard reaction is known to result in loss of nutrients, particularly that of essential amino acids; decrease in digestibility and safety issues due to the development of toxic compounds. Maillard reaction products are also known to cause oxidation of tissues and inflammation, thus increasing the risk of cardiovascular diseases and diabetes. The aim of this review is to present a detailed information about the role of foodborne constituents as antibrowning agents to significantly reduce the harmful compounds like advanced glycation end products (AGEs) during food processing. This review includes strategies involving addition of amino acids, aromatic compounds, vitamins, modification of amino acids, and reducing sugars as antibrowning agents to reduce the AGEs. The role of Food borne functional ingredients such as catechin, epicathechin, luteolin, and ferulic acids as inhibitors of AGEs is also discussed. Among the naturally occurring inhibitors, genistein could be a crucial and safe agent to reduce reactive intermediates. PRACTICAL APPLICATIONS Maillard reaction leads to changes in food color, protein functionality, protein digestibility, and loss of nutrient from foods. Maillard reaction products (MRPs) is also reported to be associated with various inflammatory conditions and may contribute to the progress of chronic diseases, including diabetes. It is hence necessary to reduce the MRPs, in both food and biological products, to offset this phenomenon. Among the strategies adopted till date, chemical agents could inhibit reactive carbonyl species and reactive oxygen species, but also are known to elicit serious side effects. Dietary flavonoids could be a very good inhibitor of MRPs both in biological and in food systems. It could be suggested that dietary flavonoids and isoflavones can be used as antibrowning agents in food and pharmaceutical industries particularly for targeted and sustained release of hypoglycemic drug in the intestines.