scholarly journals Antioxidant and Pro-Oxidant Activities of Melatonin in the Presence of Copper and Polyphenols In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 903 ◽  
Author(s):  
Jiajia Wang ◽  
Xiaoxiao Wang ◽  
Yufeng He ◽  
Lijie Jia ◽  
Chung S. Yang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hydroxyl Radical ◽  
Density Functional ◽  
Antioxidant Activities ◽  
Chelating Agent ◽  
Redox System ◽  
Radical Scavenger ◽  
Dual Function ◽  
High Concentrations

Melatonin is a well-documented antioxidant. Physicochemical analysis using the density functional theory suggests that melatonin is a copper chelating agent; however, experimental evidence is still in demand. The present study investigated the influence of melatonin on reactive oxygen species (ROS) generated from polyphenol autoxidation in the presence of copper. Surprisingly, we found that melatonin paradoxically enhanced ROS formation in a redox system containing low concentrations of copper and quercetin (Que) or (−)-epigallocatechin-3-gallate (EGCG), due to reduction of cupric to cuprous ion by melatonin. Addition of DNA to this system inhibited ROS production, because DNA bound to copper and inhibited copper reduction by melatonin. When melatonin was added to a system containing high concentrations of copper and Que or EGCG, it diminished hydroxyl radical formation as expected. Upon addition of DNA to high concentrations of copper and Que, this pro-oxidative system generated ROS and caused DNA damage. The DNA damage was not prevented by typical scavengers of hydroxyl radical DMSO or mannitol. Under these conditions, melatonin or bathocuproine disulfonate (a copper chelator) protected the DNA from damage by chelating copper. When melatonin was administered intraperitoneally to mice, it inhibited hepatotoxicity and DNA damage evoked by EGCG plus diethyldithiocarbamate (a copper ionophore). Overall, the present study demonstrates the pro-oxidant and antioxidant activities of melatonin in the redox system of copper and polyphenols. The pro-oxidant effect is inhibited by the presence of DNA, which prevents copper reduction by melatonin. Interestingly, in-vivo melatonin protects against copper/polyphenol-induced DNA damage probably via acting as a copper-chelating agent rather than a hydroxyl radical scavenger. Melatonin with a dual function of scavenging hydroxyl radical and chelating copper is a more reliable DNA guardian than antioxidants that only have a single function of scavenging hydroxyl radical.

Dietary sugars and related endogenous advanced glycation end-products increase chromosomal DNA damage in WIL2-NS cells, measured using cytokinesis-block micronucleus cytome assay

Mutagenesis ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Permal Deo ◽  
Caitlin L McCullough ◽  
Theodora Almond ◽  
Emma L Jaunay ◽  
Leigh Donnellan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Advanced Glycation End Products ◽  
Chromosomal Dna ◽  
Advanced Glycation ◽  
Age Related ◽  
Genome Damage ◽  
Glycation End Products ◽  
End Products ◽  
High Concentrations

Abstract This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu–BSA) or with fructose (Fru–BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML; 26.76 ± 1.09 nmol/mg BSA) levels in the Glu–BSA model. Nε-Carboxyethyllysine (CEL; 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1; 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru–BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu–BSA or Fru–BSA. Fructose treatment exerted a significant genotoxic dose–response effect including increases of BN with MNi (R2 = 0.7704; P = 0.0031), BN with NPBs (R2 = 0.9311; P < 0.0001) and BN with NBuds (R2 = 0.7118; P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400–600 µg/ml) induced DNA damage; however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo.

Metal ions and oxygen radical reactions in human inflammatory joint disease

1985 ◽  
Vol 311 (1152) ◽  
pp. 659-671 ◽  
Keyword(s):  
Hydroxyl Radical ◽  
Metal Ion ◽  
Tissue Injury ◽  
Copper Ion ◽  
Chelating Agent ◽  
Joint Disease ◽  
Radical Reactions ◽  
Phagocytic Cells ◽  
Bacterial Killing

Activated phagocytic cells produce superoxide (O 2 - ) and hydrogen peroxide (H 2 O 2 ) ; their production is important in bacterial killing by neutrophils and has been implicated in tissue damage by activated phagocytes. H 2 O 2 and O 2 are poorly reactive in aqueous solution and their damaging actions may be related to formation of more reactive species from them. One such species is hydroxyl radical (OH . ), formed from H 2 O 2 in the presence of iron- or copper-ion catalysts. A major determinant of the cytotoxicity of O - 2 and H 2 O 2 is thus the availability and location of metal-ion catalysts of OH* formation. Hydroxyl radical is an initiator of lipid peroxidation. Iron promoters of OH* production present in vivo include ferritin, and loosely bound iron complexes detectable by the ‘bleomycin assay’. The chelating agent Desferal (desferrioxamine B methanesulphonate) prevents iron-dependent formation of OH* and protects against phagocyte-dependent tissue injury in several animal models of human disease. The use of Desferal for human treatment should be approached with caution, because preliminary results upon human rheumatoid patients have revealed side effects. It is proposed that OH* radical is a major damaging agent in the inflamed rheumatoid joint and that its formation is facilitated by the release of iron from transferrin, which can be achieved at the low pH present in the micro-environment created by adherent activated phagocytic cells. It is further proposed that one function of lactoferrin is to protect against iron-dependent radical reactions rather than to act as a catalyst of OH· production.

Hydroxyl radical is a significant player in oxidative DNA damage in vivo

2021 ◽  
Author(s):  
Barry Halliwell ◽  
Amitava Adhikary ◽  
Michael Dingfelder ◽  
Miral Dizdaroglu
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Hydroxyl Radical ◽  
Chemical Reactions ◽  
Oxidative Dna Damage ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Schematic Representation ◽  
Important Chemical

Schematic representation of the important chemical reactions involved in reactive oxygen species-mediated DNA damage.

Ceria-Zirconia Antioxidant Nanoparticles Attenuate Hypoxia-Induced Acute Kidney Injury by Restoring Autophagy Flux and Alleviating Mitochondrial Damage

2020 ◽  
Vol 16 (7) ◽  
pp. 1144-1159
Author(s):  
Sang-Eun Hong ◽  
Jong Hun An ◽  
Seong-Lan Yu ◽  
Jaeku Kang ◽  
Chang Gyo Park ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Free Radical ◽  
Antioxidant Activities ◽  
Kidney Injury ◽  
Mitochondrial Damage ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Autophagy Flux ◽  
Novel Approach

Oxidative stress is one of the principal causes of hypoxia-induced kidney injury. The ceria nanoparticle (CNP) is known to exhibit free radical scavenger and catalytic activities. When zirconia is attached to CNPs (CZNPs), the ceria atom tends to remain in a Ce3+ form and its efficacy as a free radical scavenger thus increases. We determined the effectiveness of CNP and CZNP antioxidant activities against hypoxia-induced acute kidney injury (AKI) and observed that these nanoparticles suppress the apoptosis of hypoxic HK-2 cells by restoring autophagy flux and alleviating mitochondrial damage. In vivo experiments revealed that CZNPs effectively attenuate hypoxia-induced AKI by preserving renal structures and glomerulus function. These nanoparticles can successfully diffuse into HK-2 cells and effectively counteract reactive oxygen species (ROS) to block hypoxia-induced AKI. This suggests that these particles represent a novel approach to controlling this condition.

scholarly journals Synthesis of novel technetium-99m tricarbonyl-HBED-CC complexes and structural prediction in solution by density functional theory calculation

2019 ◽  
Vol 6 (11) ◽  
pp. 191247
Author(s):  
Shengyu Shi ◽  
Lifeng Yao ◽  
Linlin Li ◽  
Zehui Wu ◽  
Zhihao Zha ◽  
...  
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Density Functional Theory Calculation ◽  
Chelating Agent ◽  
Future Application ◽  
Stable Complex ◽  
Diacetic Acid ◽  
Functional Theory ◽  
Bifunctional Chelating Agent

HBED-CC ( N,N' -bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylene diamine- N,N' -diacetic acid, L 1 ) is a common bifunctional chelating agent in preparation of 68 Ga-radiopharmaceuticals. Due to its high stability constant for the Ga 3+ complex (logK GaL = 38.5) and its acyclic structure, it is well known for a rapid and efficient radiolabelling at ambient temperature with Gallium-68 and its high in vivo stability. [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + is an excellent precursor for radiolabelling of biomolecules. The aim of this study was to develop a novel preparation method of 99m Tc-HBED-CC complexes. In this study, HBED-CC-NI (2,2'-(ethane-1,2-diylbis((2-hydroxy-5-(3-((2-(2-nitro-1H-imidazol-1-yl)ethyl)amino)-3-oxopropyl)benzyl)-azanediyl))-diacetic acid, L 2 ), a derivative of HBED-CC, was designed and synthesized. Both L 1 and L 2 were radiolabelled by [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + successfully for the first time. In order to explore the coordination mode of metal and chelates, non-radioactive Re(CO) 3 L 1 and Re(CO) 3 L 2 were synthesized and characterized spectroscopically. Tc(CO) 3 L 1 and Tc(CO) 3 L 2 in solution were calculated by density functional theory and were analysed with radio-HPLC chromatograms. It showed that [ 99m Tc]Tc(CO) 3 L 2 forms two stable diastereomers in solution, which is similar to those of [ 68 Ga]Ga-HBED-CC complexes. Natural bond orbital analysis through the natural population charges revealed a charge transfer between [ 99m Tc][Tc(CO) 3 ] + and L 1 or L 2 . The experimental results showed that tricarbonyl technetium might form stable complex with HBED-CC derivatives, which is useful for the future application of using HBED-CC as a bifunctional chelating agent in developing new 99m Tc-radiopharmaceuticals as diagnostic imaging agents.

scholarly journals Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide

1991 ◽  
Vol 273 (3) ◽  
pp. 601-604 ◽  
Author(s):  
O I Aruoma ◽  
B Halliwell ◽  
E Gajewski ◽  
M Dizdaroglu
Keyword(s):  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Copper Ion ◽  
Nitrilotriacetic Acid ◽  
Dna Bases ◽  
Radical Scavenger ◽  
Base Damage

Mixtures of Cu2+ and H2O2 at pH 7.4 caused damage to the bases in DNA greater than that caused by mixtures of Fe3+ and H2O2. Addition of ascorbic acid to the Cu2+/H2O2 system caused a very large increase in base damage, much greater than that produced by the Fe3+/H2O2/ascorbic acid system. The products of base damage in the presence of Cu2+ were typical products that have been shown to result from attack of hydroxyl radicals upon the DNA bases. Cytosine glycol, thymine glycol, 8-hydroxyadenine and especially 8-hydroxyguanine were the major products in both the Cu2+/H2O2 and the Cu2+/H2O2/ascorbic acid systems. Base damage in DNA by these systems was inhibited by the chelating agents EDTA and nitrilotriacetic acid and by catalase, but not by superoxide dismutase, nor by the hydroxyl-radical scavenger mannitol. It is proposed that Cu2+ ions bound to the DNA react with H2O2 and ascorbic acid to generate hydroxyl radicals, which then immediately attack the DNA bases in a site-specific manner. A hypoxanthine/xanthine oxidase system also caused damage to the DNA bases in the presence of Cu2+ ions. This was inhibited by superoxide dismutase and catalase. The high activity of Cu2+ ions, when compared with Fe3- ions, in causing hydroxyl-radical-dependent damage to DNA and to other biomolecules, means that the availability of Cu2+ ions in vivo must be carefully controlled.

scholarly journals The deleterious effects induced by an acute exposure of human skin to common air pollutants are prevented by extracts of Deschampsia antarctica

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra Fernández-Martos ◽  
María I. Calvo-Sánchez ◽  
Ana Lobo-Aldezabal ◽  
Ana Isabel Sánchez-Adrada ◽  
Carmen Moreno ◽  
...  
Keyword(s):  
Human Skin ◽  
Air Pollutants ◽  
Redox System ◽  
Acute Exposure ◽  
Deschampsia Antarctica ◽  
Innovative Strategies ◽  
Pre Treatment ◽  
Human Ecosystems ◽  
High Concentrations

AbstractThe homeostatic and regenerative potential of the skin is critically impaired by an increasing accumulation of air pollutants in human ecosystems. These toxic compounds are frequently implicated in pathological processes such as premature cutaneous ageing, altered pigmentation and cancer. In this scenario, innovative strategies are required to tackle the effects of severe air pollution on skin function. Here we have used a Human Skin Organotypic Culture (HSOC) model to characterize the deleterious effects of an acute topic exposure of human skin to moderately high concentrations of common ambient pollutants, including As, Cd, Cr, dioxins and tobacco smoke. All these toxic compunds inflict severe damage in the tissue, activating the AHR-mediated response to xenobiotics. We have further evaluated the potential of an aqueous leaf extract of the polyextremophile plant Deschampsia antarctica (Edafence) to protect human skin against the acute exposure to toxic pollutants. Our results indicate that pre-treatment of HSOC samples with this aqueous extract conuterbalances the deleterious effects of the exposure to toxic comunds and triggers the activation of key genes invoved in the redox system and in the pro-inflammatory/wound healing response in the skin, suggesting that this natural compound might be effectively used in vivo to protect human skin routinely in different daily conditions.

In vivo Effect of Hydroxyl Radical Scavenger on Methylguanidine Production from Creatinine

Nephron ◽  
1997 ◽  
Vol 75 (1) ◽  
pp. 103-105 ◽  
Author(s):  
Takako Yokozawa ◽  
Naoki Fujitsuka ◽  
Hikokichi Oura ◽  
Kazuharu Ienaga ◽  
Ko Nakamura
Keyword(s):  
Hydroxyl Radical ◽  
Radical Scavenger ◽  
Hydroxyl Radical Scavenger

scholarly journals Reviews on Mechanisms ofIn VitroAntioxidant Activity of Polysaccharides

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Junqiao Wang ◽  
Shuzhen Hu ◽  
Shaoping Nie ◽  
Qiang Yu ◽  
Mingyong Xie
Keyword(s):  
Antioxidant Activities ◽  
Cell Structure ◽  
Free Radical Scavenger ◽  
Antioxidant Systems ◽  
Radical Scavenger ◽  
Significant Damage ◽  
Nonenzymatic Antioxidants ◽  
Underlying Mechanisms

It is widely acknowledged that the excessive reactive oxygen species (ROS) or reactive nitrogen species (RNS) induced oxidative stress will cause significant damage to cell structure and biomolecular function, directly or indirectly leading to a number of diseases. The overproduction of ROS/RNS will be balanced by nonenzymatic antioxidants and antioxidant enzymes. Polysaccharide or glycoconjugates derived from natural products are of considerable interest from the viewpoint of potentin vivoandin vitroantioxidant activities recently. Particularly, with regard to thein vitroantioxidant systems, polysaccharides are considered as effective free radical scavenger, reducing agent, and ferrous chelator in most of the reports. However, the underlying mechanisms of these antioxidant actions have not been illustrated systematically and sometimes controversial results appeared among various literatures. To address this issue, we summarized the latest discoveries and advancements in the study of antioxidative polysaccharides and gave a detailed description of the possible mechanisms.

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