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1.
Radicals, Oxidative/Nitrosative Stress and Preeclampsia.
Taysi, S, Tascan, AS, Ugur, MG, Demir, M
Mini reviews in medicinal chemistry. 2019;(3):178-193
Abstract
Preeclampsia (PE) has a profound effect in increasing both maternal and fetal morbidity and mortality especially in third World. Disturbances of extravillous trophoblast migration toward uterine spiral arteries is characteristic feature of PE, which, in turn, leads to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Underlying pathogenesis appeared to be an altered bioavailability of nitric oxide (NO•) and tissue damage caused by increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The increase in ROS and RNS production or the decrease in antioxidant mechanisms generates a condition called oxidative and nitrosative stress, respectively, defined as the imbalance between pro- and antioxidants in favor of the oxidants. Additionally, ROS might trigger platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. As a consequence of these disorders could result in deficiencies in oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the one hand, enzymatic and nonenzymatic antioxidants scavenge ROS and protect tissues against oxidative damage. More specifically, placental antioxidant enzymes including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) protect the vasculature from ROS, maintaining the vascular function. On the other hand, ischemia in placenta in PE reduces the antioxidant activity. Collectively, the extent of oxidative stress would increase and therefore leads to the development of the pathological findings of PE including hypertension and proteinuria. Our goal in this article is to review current literature about researches demonstrating the interplay between oxidative, nitrosative stresses and PE, about their roles in the pathophysiology of PE and also about the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation.
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2.
Fast reaction of carbon free radicals with flavonoids and other aromatic compounds.
Nauser, T, Gebicki, JM
Archives of biochemistry and biophysics. 2019;:108107
Abstract
Many theoretical and experimental studies have shown that the principal initial biological targets of free radicals are nucleic acids, lipids and proteins. The reaction normally generates carbon-centered radicals which can propagate molecular damage either directly or after formation of new reactive species following reaction with oxygen. Overall damage prevention is therefore best achieved by repair of the carbon radicals before they initiate further reactions. Recent studies have shown that the repair cannot be achieved by normal levels of the endogenous antioxidants glutathione, ascorbate or urate. Since their concentrations are well regulated and cannot be enhanced by oral intake, we have investigated the effectiveness of flavonoids and other polyphenols as potential carbon radical repair agents, because their levels in vivo can be significantly enhanced by diet. Pulse radiolysis measurements of the rate constants of repair of amino acid radicals by several polyphenols showed reversible formation of radical-polyphenol adducts 100-1000 times faster than previously reported for the bimolecular stoichiometric reactions of flavonoids i.e. with rate constants in the order of 1010 M-1s-1. Adduct formation depended only on the presence of a carbon-centered radical and an aromatic moiety in the reactants, without the involvement of redox reactions at the phenolic groups. Formation of adducts lowered the reactivity of the radicals. Our results suggest that flavonoids, polyphenols and many of their metabolites can effectively reduce the damaging potential of carbon radicals at concentrations achievable in vivo by diets rich in fruits and vegetables.
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3.
Pulse Radiolysis Studies for Mechanism in Biochemical Redox Reactions.
Kobayashi, K
Chemical reviews. 2019;(6):4413-4462
Abstract
Pulse radiolysis is a powerful method for generating highly reduced or oxidized species and free radicals. Combined with fast time-resolved spectroscopic measurement, we can monitor the reactions of intermediate species on time scales ranging from picoseconds to seconds. The application of pulse radiolysis to water generates hydrated electrons (eaq-) and specific radicals, rendering this technique useful for investigating a number of biological redox processes. The first pulse radiolysis redox investigations explored in this review involved intramolecular electron transfer processes in protein with multiple electron-accepting sites. Pulse radiolysis enabled direct monitoring of the internal electron transfer rates and the distribution of electrons within proteins. Structural information from X-ray data has allowed analysis of the rate constants and their activation parameters in relation to the mechanisms with current theoretical treatments. The second set of pulse radiolysis redox investigations explored here concerned the intermediates of enzyme reactions after redox reactions. Pulse radiolysis allowed the extremely rapid donation of electrons to a redox center in a protein. It makes it possible to observe the unstable intermediates after the reduction and the following subsequent steps. For example, the intermediates generated through the one-electron reduction of oxygenated hemoproteins, such as cytochrome P450 and nitric oxide synthase, were characterized. Interestingly, ligand exchange can occur upon the reduction of heme iron, in which different amino acid residues bind to heme in the ferrous and ferric states, respectively. We directly observed the ligand-switching intermediates of bacterial CooA, a CO sensor, and bacterial iron response regulator protein. These ligand exchange processes are physiologically important for regulating the electrode potential and effective formation of superoxide anion or HO•. The third set of pulse radiolysis redox investigations explored in this review concerns free-radical processes in biological systems. Free radicals are produced in cells and organisms in a variety of processes. The cell has developed special and very effective machinery for controlling and detoxifying reactive radicals. Radiation-generated radicals allow studies of the reactions between specific radicals and solutes, often revealing the mechanisms underlying the initial and subsequent reactions. The crucial contribution was made using pulse radiolysis techniques and knowledge of the identities, properties, and reactions of radicals. These radicals include superoxide (O2•-), nitric monoxide (NO•), ascorbate, urate, and protein radicals. This review focuses on the reactions of these radicals and their physiological functions.
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4.
The effects of ketamine and lidocaine on free radical production after tourniquet-induced ischemia-reperfusion injury in adults.
Peker, K, Ökesli, S, Kıyıcı, A, Deyişli, C
Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES. 2019;(2):111-117
Abstract
BACKGROUND The primary aim of this study was to compare the effects of a small-dose infusion of 2 antioxidant agents, ketamine and lidocaine, on ischemia-reperfusion injury (IRI) in patients undergoing elective lower limb surgery. Ischemia-modified albumin (IMA), lactate, and blood gas levels were all measured and assessed. METHODS A total of 100 patients who underwent lower extremity surgery were randomized into 3 groups. After spinal anesthesia, the ketamine group (Group K, n=33) was given a ketamine infusion, a lidocaine infusion was administered to the lidocaine group (Group L, n=33), and in the control group (Group C), 0.9% a sodium chloride infusion was performed. Blood samples were obtained for IMA analysis before anesthetic administration (baseline), at 30 minutes of tourniquet inflation (ischemia), and 15 minutes after tourniquet deflation (reperfusion). Arterial blood gas measurements were determined before anesthetic administration and 15 minutes after tourniquet deflation. RESULTS The lactate and IMA levels at reperfusion were significantly lower in both the ketamine group and the lidocaine group when compared with the control group. CONCLUSION The administration of both ketamine and lidocaine infusions significantly decreased skeletal muscle IRI-related high lactate and IMA levels. These results suggest the possibility of the clinical application of ketamine or lidocaine infusions in cases of skeletal muscle-related IRI.
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5.
Evolutionary adaptations that enable enzymes to tolerate oxidative stress.
Imlay, JA, Sethu, R, Rohaun, SK
Free radical biology & medicine. 2019;:4-13
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Abstract
Biochemical mechanisms emerged and were integrated into the metabolic plan of cellular life long before molecular oxygen accumulated in the biosphere. When oxygen levels finaly rose, they threatened specific types of enzymes: those that use organic radicals as catalysts, and those that depend upon iron centers. Nature has found ways to ensure that such enzymes are still used by contemporary organisms. In some cases they are restricted to microbes that reside in anoxic habitats, but in others they manage to function inside aerobic cells. In the latter case, it is frequently true that the ancestral enzyme has been modified to fend off poisoning. In this review we survey a range of protein adaptations that permit radical-based and low-potential iron chemistry to succeed in oxic environments. In many cases, accessory domains shield the vulnerable radical or metal center from oxygen. In others, the structures of iron cofactors evolved to less oxidizable forms, or alternative metals replaced iron altogether. The overarching view is that some classes of biochemical mechanism are intrinsically incompatible with the presence of oxygen. The structural modification of target enzymes is an under-recognized response to this problem.
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The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela.
Cardone, RA, Alfarouk, KO, Elliott, RL, Alqahtani, SS, Ahmed, SBM, Aljarbou, AN, Greco, MR, Cannone, S, Reshkin, SJ
International journal of molecular sciences. 2019;(15)
Abstract
Cancer cells have an unusual regulation of hydrogen ion dynamics that are driven by poor vascularity perfusion, regional hypoxia, and increased glycolysis. All these forces synergize/orchestrate together to create extracellular acidity and intracellular alkalinity. Precisely, they lead to extracellular pH (pHe) values as low as 6.2 and intracellular pH values as high as 8. This unique pH gradient (∆pHi to ∆pHe) across the cell membrane increases as the tumor progresses, and is markedly displaced from the electrochemical equilibrium of protons. These unusual pH dynamics influence cancer cell biology, including proliferation, metastasis, and metabolic adaptation. Warburg metabolism with increased glycolysis, even in the presence of Oxygen with the subsequent reduction in Krebs' cycle, is a common feature of most cancers. This metabolic reprogramming confers evolutionary advantages to cancer cells by enhancing their resistance to hypoxia, to chemotherapy or radiotherapy, allowing rapid production of biological building blocks that support cellular proliferation, and shielding against damaging mitochondrial free radicals. In this article, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression, adaptation, and in determining the programming and re-programming of tumor cell metabolism.
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The Free Radical Diseases of Prematurity: From Cellular Mechanisms to Bedside.
Perrone, S, Santacroce, A, Longini, M, Proietti, F, Bazzini, F, Buonocore, G
Oxidative medicine and cellular longevity. 2018;:7483062
Abstract
During the perinatal period, free radicals (FRs) are involved in several physiological roles such as the cellular responses to noxia, the defense against infectious agents, the regulation of cellular signaling function, and the induction of a mitogenic response. However, the overproduction of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS) which represents a deleterious process and an important mediator of damage to the placenta and the developing fetus. After birth, OS can be magnified by other predisposing conditions such as hypoxia, hyperoxia, ischemia, hypoxia ischemia-reperfusion, inflammation, and high levels of nonprotein-bound iron. Newborns are particularly susceptible to OS and oxidative damage due to the increased generation of FRs and the lack of adequate antioxidant protection. This impairment of the oxidative balance has been thought to be the common factor of the so-called "free radical related diseases of prematurity," including retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, kidney damage, and oxidative hemolysis. In this review, we provide an update focused on the factors influencing these diseases refining the knowledge about the role of OS in their pathogenesis and the current evidences of such relationship. Mechanisms governing FR formation and subsequent OS may represent targets for counteracting tissue damage.
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8.
Sources of free radicals and oxidative stress in the oral cavity.
Żukowski, P, Maciejczyk, M, Waszkiel, D
Archives of oral biology. 2018;:8-17
Abstract
OBJECTIVE An oral cavity is a place especially susceptible to oxidative damage. It is subjected to many environmental pro-oxidative factors or factors that have the ability to generate reactive oxygen species (ROS). The aim of this article is to present the main sources of ROS and oxidative stress in the oral environment. DESIGN A literature search was performed using the PubMed and Google Scholar databases. RESULTS One of the most important ROS sources in the oral cavity is periodontal inflammation. Other sources of ROS include: xenobiotics (ethanol, cigarette smoke, drugs), food (high-fat diet, high-protein diet, acrolein), dental treatment (ozone, ultrasound, non-thermal plasma, laser light, ultraviolet light), and dental materials (fluorides, dental composites, fixed orthodontic appliances, and titanium fixations). It has been shown that excessive production of ROS in the oral cavity may cause oxidative stress and oxidative damage to cellular DNA, lipids, and proteins, thus predisposing to many oral and systemic diseases. CONCLUSIONS Recognition of the exogenous sources of ROS and limitation of exposure to the ROS generating factors can be one of the prophylactic measures preventing oral and systemic diseases. It is suggested that antioxidant supplementation may be helpful in people exposed to excessive production of ROS in the oral cavity system.
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Selenoproteins are involved in antioxidant defense systems in thalassemia.
Genc, GE, Ozturk, Z, Gumuslu, S
Metallomics : integrated biometal science. 2017;(9):1241-1250
Abstract
Thalassemia major (TM) is a hereditary blood disease that affects the production of hemoglobin, resulting in severe anemia. Iron overload because of repeated blood transfusion and increased intestinal iron absorption and hemolysis are the major causes of increased oxidative stress in these patients. Growth and maturational delay, cardiomyopathy, endocrinopathies, and osteoporosis are the complications of thalassemia, secondary to anemia and iron overload. The human body has endogenous defense mechanisms to help protect against free radical-induced cell damage. Selenoproteins are important enzymes involved in these antioxidant defense mechanisms. In thalassemia patients, selenoproteins are essential because of their potential defense against oxidative damage due to iron overload and hemolysis. The aim of this review is to provide an overview of data regarding selenoproteins including glutathione peroxidase, thioredoxin reductase and iodothyronine deiodinases in TM patients. We also underline some complications of thalassemia that may be associated with selenoproteins.
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Evaluation of plasma oxidative stress, with or without antioxidant supplementation, in superficial partial thickness burn patients: a pilot study.
Raposio, E, Grieco, MP, Caleffi, E
Journal of plastic surgery and hand surgery. 2017;(6):393-398
Abstract
BACKGROUND Oxidative stress is one of the main causes of pathophysiological alterations observed during burn injury. The present pilot study aimed to determine whether a specific oral antioxidant supplementation could in any way influence free radical blood values in patients affected by superficial partial thickness burns. MATERIALS AND METHODS Plasma oxidants and plasma antioxidant capacity were analysed in 20 superficial partial thickness burn patients for a 2-week period; patients were randomly divided into two groups, one of which was supported with a specifically designed oral antioxidant formula (Squalene 100 mg, Vitamin C 30 mg, Coenzyme Q10 10 mg, Zinc 5 mg, Beta Carotene 3.6 mg, Bioflavonoids 30 mg, Selenium 55 mcg) administered daily, starting from the day of admission, for the whole study period. RESULTS No significant differences were found in plasma oxidants and plasma antioxidant capacity between the two groups of patients. CONCLUSIONS These results did not reflect any significant benefits of an antioxidant oral supplementation at usual dosages when considering oxidative plasmatic values of superficial partial thickness burn patients.