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1.
Copper environmental toxicology, recent advances, and future outlook: a review.
Rehman, M, Liu, L, Wang, Q, Saleem, MH, Bashir, S, Ullah, S, Peng, D
Environmental science and pollution research international. 2019;(18):18003-18016
Abstract
Copper (Cu) is one of the micronutrients needed by living organisms. In plants, Cu plays key roles in chlorophyll formation, photosynthesis, respiratory electron transport chains, oxidative stress protection as well as protein, carbohydrate, and cell wall metabolism. Therefore, deficiency of Cu can alter various functions of plant metabolism. However, Cu-based agrochemicals have traditionally been used in agriculture and being excessively released into the environment by anthropogenic activities. Continuous and extensive release of Cu is an imperative issue with various documented cases of phytotoxicity by the overproduction of reactive oxygen species (ROS) and damage to carbohydrates, lipids, proteins, and DNA. The mobility of Cu from soil to plant tissues has several concerns including its adverse effects on humans. In this review, we have described about importance and occurrence of Cu in environment, Cu homeostasis and toxicity in plants as well as remediation and progress in research so far done worldwide in the light of previous findings. Furthermore, present review provides a comprehensive ecological risk assessment on Cu in soils and thus provides insights for agricultural soil management and protection.
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2.
Ibuprofen as a corrosion inhibitor for copper in synthetic acid rain solution.
Tasić, ZZ, Mihajlović, MBP, Simonović, AT, Radovanović, MB, Antonijević, MM
Scientific reports. 2019;(1):14710
Abstract
It is known that if unused drugs are improperly disposed, they can pollute the environment. Furthermore, researchers are still trying to find an environmentally friendly corrosion inhibitor. These factors lead to the possible application of unused pharmaceutical compounds as corrosion inhibitors. The feasibility of an anti-inflammatory, analgesic and antipyretic drug, ibuprofen, was evaluated as a potential copper corrosion inhibitor in synthetic acid rain solution. This investigation was performed by applying electrochemical and weight loss measurements and quantum chemical calculations. The results obtained by these techniques revealed the ability of ibuprofen to protect copper from corrosion. The inhibition efficiency of ibuprofen rises with increase in its concentration and can reach a value of 97.3%. The results of surface analysis of treated coupons by scanning electron microscopy and theoretical calculations are consistent with the experimental results.
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3.
Role of copper and ketamine in major depressive disorder - an update.
Słupski, J, Słupska, A, Szałach, ŁP, Włodarczyk, A, Górska, N, Szarmach, J, Jakuszkowiak-Wojten, K, Gałuszko-Węgielnik, M, Wilkowska, A, Wiglusz, MS, et al
Psychiatria Danubina. 2019;(Suppl 3):520-523
Abstract
Major depressive disorder is one of the most important psychiatric issues worldwide, with important prevalence of treatment-resistant depression (TRD). Non-monoaminergic agents are currently in the spotlight. Objective was to explore for information about mechanisms of action of ketamine, its connections with copper and possible importance for TRD treatment. There are at least few possible pathways for ketamine action in depression in which copper and other divalent ions may show a vital role. There is urgent need for more studies to gather information about correlation between ketamine, copper and antidepressive features of these agents.
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4.
Copper and Neurotoxicity in Autism Spectrum Disorder.
Santos, G, Borges, JMP, Avila-Rodriguez, M, Gaíno, SB, Barreto, GE, Rúbio, ÉP, Aguiar, RM, Galembeck, E, Bromochenkel, CB, de Oliveira, DM
Current pharmaceutical design. 2019;(45):4747-4754
Abstract
Free radicals (FR) act on living organisms and present unpaired electrons in the molecular orbitals of oxygen or nitrogen species. They are classified as redox reactions and account for a wide range of processes in biological systems. Genetic and environmental factors may alter the levels of FR in the cell, leading to deleterious consequences such as membrane lipid peroxidation, protein nitration, enzyme, carbohydrate and DNA damage, ultimately resulting in premature aging and a pro-inflammatory microenvironment as observed in Alzheimer's disease (AD) and autism spectrum disorder (ASD). O2 radical ability to act as a Lewis base and to form a complex with metal transition such as iron and copper (Lewis acids) leads to biomolecules oxidation at physiological pH, thus increasing the possibility of injury and oxidative damage in biological tissues. In this review, we discuss the role of metals, like copper, and the amyloid precursor protein (APP) derivative (s-APP-alpha) as an antioxidant and a possible adjuvant in the treatment of some autistic spectrum disorder symptoms (ASD).
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5.
Mechanisms of sublethal copper toxicity damage to the photosynthetic apparatus of Rhodospirillum rubrum.
Jaime-Pérez, N, Kaftan, D, Bína, D, Bokhari, SNH, Shreedhar, S, Küpper, H
Biochimica et biophysica acta. Bioenergetics. 2019;(8):640-650
Abstract
Magnesium (Mg2+) is the ubiquitous metal ion present in chlorophyll and bacteriochlorophyll (BChl), involved in photosystems in photosynthetic organisms. In the present study we investigated targets of toxic copper binding to the photosynthetic apparatus of the anoxygenic purple bacterium Rhodospirillum rubrum. This was done by a combination of in vivo measurements of flash photolysis and fast fluorescence kinetics combined with the analysis of metal binding to pigments and pigment-protein complexes isolated from Cu-stressed cells by HPLC-ICPMS (ICP-sfMS). This work concludes that R. rubrum is highly sensitive to Cu2+, with a strong inhibition of the photosynthetic reaction centres (RCs) already at 2 μM Cu2+. The inhibition of growth and of RC activity was related to the formation of Cu-containing BChl degradation products that occurred much more in the RC than in LH1. These results suggest that the shift of metal centres in BChl from Mg2+ to Cu2+ can occur in vivo in the RCs of R. rubrum under environmentally realistic Cu2+ concentrations, leading to a strong inhibition of the function of these RCs.
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6.
The Effect of Curcumin on Serum Copper and Zinc and Zn/Cu Ratio in Individuals with Metabolic Syndrome: A Double-Blind Clinical Trial.
Safarian, H, Parizadeh, SMR, Saberi-Karimain, M, Darroudi, S, Javandoost, A, Mohammadi, F, Moammeri, M, Ferns, GA, Ghayour-Mobarhan, M, Mohebati, M
Journal of dietary supplements. 2019;(6):625-634
Abstract
Metabolic syndrome is a complex disorder with high socioeconomic costs and a high global prevalence. The serum concentrations of some trace elements are higher in people with metabolic syndrome compared to normal individuals. Curcumin is derived from turmeric and has antioxidant and anti-inflammatory properties. Curcumin may therefore have a potential role in the management of cardiovascular risk. The aim of this study was to investigate the effects of curcumin on serum copper (Cu), zinc (Zn), and Zn/Cu ratio levels in patients with metabolic syndrome. A double-blind clinical trial was designed in which 120 individuals with metabolic syndrome were randomly assigned to one of three groups: curcumin 1gr/day, phospholipidated curcumin 1gr/day, or a placebo, each taken for 6 weeks. Serum copper and zinc were measured before and after intervention. At baseline, in addition to obtaining the anthropometric characteristics of participants, a fasting blood sample was taken from each participant, and the concentrations of serum Cu and Zn were measured by atomic absorption (Varian AA 240 FS model). Serum Zn concentrations rose significantly in the phospholipidated curcumin and curcumin groups, being significantly higher (p <.001) in the phospholipidated curcumin group than in the curcumin group (p <.05). Serum Zn concentration fell in the control group (p <.05). Changes in serum Zn level from baseline to the levels after six weeks' intervention were significantly different between the groups, but changes in serum Cu from between baseline until after intervention were not significantly different. The serum Zn/Cu level in phospholipidated curcumin and curcumin groups after intervention was higher than for the control group, but it was more significant in the group taking phospholipidated curcumin (p <.001). Curcumin and phospholipidated curcumin complex, given at a dose of 1 g per day for six weeks, were associated with an increase in serum zinc and consequently zinc-to-copper ratio.
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7.
Copper Depletion as a Therapeutic Strategy in Cancer.
Lopez, J, Ramchandani, D, Vahdat, L
Metal ions in life sciences. 2019
Abstract
Copper is an essential trace element that plays a critical role in a variety of basic biological functions, and serves as a key component in a number of copper-dependent enzymes that regulate such processes as cell proliferation, angiogenesis, and motility. A growing body of preclinical work has demonstrated that copper is essential to metastatic cancer progression, and may have a role in tumor growth, epithelial-mesenchymal transition, and the formation of the tumor microenvironment and pre-metastatic niche. As a result, copper depletion has emerged as a novel therapeutic strategy in the treatment of metastatic cancer. We present a review of the physiologic role of copper with a discussion of relevant enzymes of the copper proteome in both normal tissue and in cancer. We conducted a comprehensive review of the available preclinical data of several copper chelation agents, including penicillamine, trientine, disulfiram, clioquinol, and tetrathiomolybdate (TM), across a variety of tumor types. We also present the existing early phase clinical trial data for the use of the copper chelator TM in the treatment of breast cancer and other malignancies.
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8.
Plasma copper and the risk of first stroke in hypertensive patients: a nested case-control study.
Zhang, J, Cao, J, Zhang, H, Jiang, C, Lin, T, Zhou, Z, Song, Y, Li, Y, Liu, C, Liu, L, et al
The American journal of clinical nutrition. 2019;(1):212-220
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Abstract
BACKGROUND Previous studies indicated that trace elements may play an important role in cardiovascular diseases. However, data concerning the association between blood copper and the risk of stroke are limited. OBJECTIVE The aim of this study was to evaluate the association between plasma copper and the risk of first stroke, and examine any possible effect modifiers in hypertensive patients. METHODS We conducted a nested case-control study, using data from the China Stroke Primary Prevention Trial. Hypertension is defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or taking antihypertensive medication. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. The crude and adjusted risks of first stroke were estimated by ORs and 95% CIs using conditional logistic regression, without or with adjusting for pertinent covariates, respectively. RESULTS There were significant positive associations of plasma copper with risk of first stroke (per SD increment-OR: 1.20; 95% CI: 1.03, 1.39) and first ischemic stroke (OR: 1.26; 95% CI: 1.07, 1.50). When plasma copper was categorized in quartiles, significantly higher risks of first stroke (OR: 1.72; 95% CI: 1.12, 2.65) and first ischemic stroke (OR: 1.91; 95% CI: 1.18, 3.11) were found in participants in quartile 4 (≥ 117.0 μg/dL) than in those in quartile 1 (< 91.2 μg/dL). Furthermore, the plasma copper-first stroke association was significantly stronger in participants with higher BMI (< 25.0 compared with ≥ 25.0 kg/m2, P-interaction = 0.024). However, there was no significant association between plasma copper and first hemorrhagic stroke. CONCLUSIONS In Chinese hypertensive patients, there was a significant positive association between baseline plasma copper and the risk of first stroke, especially among those with higher BMI.This trial was registered at clinicaltrials.gov as NCT00794885.
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9.
Cellular and sub-cellular Cu isotope fractionation in the human neuroblastoma SH-SY5Y cell line: proliferating versus neuron-like cells.
Costas-Rodríguez, M, Colina-Vegas, L, Solovyev, N, De Wever, O, Vanhaecke, F
Analytical and bioanalytical chemistry. 2019;(19):4963-4971
Abstract
Cu isotope fractionation was investigated in the human neuroblastoma SH-SY5Y cell line, in a proliferating/tumor phase (undifferentiated cells), and in a differentiated state (neuron-like cells), induced using retinoic acid (RA). The SH-SY5Y cell line displays genetic aberrations due to its cancerous origin, but differentiation drives the cell line towards phenotypes suitable for the research of neurological diseases (e.g., Alzheimer's disease or Parkinson's disease). Cellular Cu distribution was first explored by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging and, subsequently, Cu isotopic analysis was performed at cellular and sub-cellular levels via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). The SH-SY5Y cells showed a re-distribution of intracellular Cu upon RA differentiation. Both undifferentiated and differentiated cells became systematically enriched in the light 63Cu isotope with increasing intracellular Cu content. Differentiated neuron-like SH-SY5Y cells showed a heavier Cu isotopic composition (+ 0.3‰) than did the undifferentiated proliferating cells when exposed to Cu for 24 h. However, after a longer exposure time (72 h), no difference was observed between both cellular phenotypes. Mitochondrial fractions were enriched in the light 63Cu isotope, compared to whole cells, for both undifferentiated and differentiated cells (no significant difference). The Cu isotopic composition of the remaining cell lysates was heavier than that of the whole cells and + 0.2‰ heavier in the differentiated cells than in the undifferentiated cells. These results indicate that neuronal differentiation affects the Cu isotope fractionation accompanying Cu uptake in the cells, but this effect does not seem to be associated with the mitochondrial Cu pathway. Cu isotope fractionation can be an interesting tool for studying Cu metabolism at a (sub)-cellular level in functional neurons. Graphical abstract.
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10.
Mechanistically Guided Predictive Models for Ligand and Initiator Effects in Copper-Catalyzed Atom Transfer Radical Polymerization (Cu-ATRP).
Fang, C, Fantin, M, Pan, X, de Fiebre, K, Coote, ML, Matyjaszewski, K, Liu, P
Journal of the American Chemical Society. 2019;(18):7486-7497
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Abstract
Copper-catalyzed atom transfer radical polymerization (Cu-ATRP) is one of the most widely used controlled radical polymerization techniques. Notwithstanding the extensive mechanistic studies in the literature, the transition states of the activation/deactivation of the growing polymer chain, a key equilibrium in Cu-ATRP, have not been investigated computationally. Therefore, the understanding of the origin of ligand and initiator effects on the rates of activation/deactivation is still limited. Here, we present the first computational analysis of Cu-ATRP activation transition states to reveal factors that affect the rates of activation and deactivation. The Br atom transfer between the polymer chain and the Cu catalyst occurs through an unusual bent geometry that involves pronounced interactions between the polymer chain end and the ancillary ligand on the Cu catalyst. Therefore, the rates of activation/deactivation are determined by both the electronic properties of the Cu catalyst and the ligand-initiator steric repulsions. In addition, our calculations revealed the important role of ligand backbone flexibility on the activation. These theoretical analyses led to the identification of three chemically meaningful descriptors, namely HOMO energy of the catalyst ( EHOMO), percent buried volume ( Vbur%), and distortion energy of the catalyst (Δ Edist), to describe the electronic, steric, and flexibility effects on reactivity, respectively. A robust and simple predictive model for ligand effect on reactivity is thereby established by correlating these three descriptors with experimental activation rate constants using multivariate linear regression. Validation using a structurally diverse set of ligands revealed the average error is less than ±2 kcal/mol compared to the experimentally derived activation energies. The same approach was also applied to develop a predictive model for reactivity of different alkyl halide initiators using R-X bond dissociation energy (BDE) and Cu-X halogenophilicity as descriptors.