Copper Ion Toxicity Research Articles

Inhibitory Effect of Combined Exposure to Copper Ions and Polystyrene Microplastics on the Growth of Skeletonema costatum

As two significant pollutants, the increased concentrations of copper ions and microplastics in coastal waters pose a substantial threat to the health of marine ecosystems. This study explored the individual and combined toxic effects of copper ions and microplastics on the marine diatom Skeletonema costatum. The results indicated that copper ions at a concentration of 0.05 mg/L exerted a negative impact on the growth of S. costatum; however, the influence of microplastics on algal cell growth was more complex: there was no significant inhibition of algal cell growth observed within the first 72 h of cultivation, but a pronounced negative effect on cell growth was noted between 72 and 96 h, with high concentrations (10.00 mg/L) of microplastics even causing a premature stagnation phase in algal cell growth. When both pollutants were present simultaneously, their impact on cell growth was similar to that of the microplastic pollution group, yet the growth condition was better than that of the copper ion pollution group. Through investigation of adsorption rates and toxicity mitigation rates, it was found that the adsorption of copper ions by microplastics was a significant reason for the improved growth condition of algal cells in the mixed pollution group compared to the copper ion pollution group. However, in the later stages of cultivation, the inhibitory effect of microspheres on algal cell growth counteracted their mitigating effect on copper ion toxicity. This study provides a reference for evaluating the impact of microplastics and heavy metals on coastal ecosystem health and for revealing the interactions between different pollutants.

Molecular receptors integrated bimodal porous polymer scaffolds as portable solid-state optical ion-sensors and extractors for the selective capturing of ultra-trace toxic copper ions

BackgroundEnvironmental contamination by heavy metal ions has caused growing ecological and public health concerns. In this line, monitoring of copper toxicity gains importance due to its application in industrial, agricultural, domestic, medical and technological sectors. Although noteworthy breakthroughs were made, critical issues, such as portability, the need for well-trained personnel, costly/complex instrumentations, long response time, and the introduction of secondary contaminants, required attention. Hence, developing a low-cost, user-friendly, real-time, portable analytical platform for rapid and on-site analysis remained imperative. Solid-state colorimetric sensors have gained widespread popularity due to their low cost, ease of use, and brilliant sensitivity/selectivity. ResultsWe have successfully unfolded an ultra-portable azomethine-infused structurally interwoven polymer monolith as the solid-state chromatic sensor for the quantitative naked-eye detection of ultra-trace Cu2+ in industrial/environmental samples. For the sensor fabrication, non-hygroscopic conjugated Schiff-base receptors, namely N-(1E,2E)-3-(4-dimethylamino)phenyl)allylidene)-3-nitrobenzohydrazide (DPAN) and 2,3-bis(((1E,2E)-3-(4-dimethylamino)phenyl)allylidene)amino)malononitrile (DPAM) were synthesized in-house and voluminously immobilized onto a crack-free porous poly(4VP-co-EGDMA) monolith framework. The topological structure and functionalities of the porous polymer monolith and chromatic sensor materials were examined using various surface analytical and microscopic techniques. The excellent surface area and intriguing interlaced porosity features of the tailor-made polymer monolith facilitated the voluminous anchoring of the chromatic receptors for the selective/sensitive targeting of Cu2+. The DPAN and DPAM receptor-loaded poly(4VP-co-EGDMA) sensors exhibited a linear range of 0–150 μg/L, with the limit of detection of 0.11 and 0.13 μg/L for Cu2+, respectively. The sensors manifested Cu2+ specificity amidst concomitant matrix ions to highlight the relevance of the proposed solid-state sensor. SignificanceThe sensor materials offered a reliable approach for detecting and quantifying environmentally toxic and industrially pertinent Cu2+ from aqueous samples, with the prospect of large-scale production, owing to the sensor's integrated compact design that can be reused for repeated real-time surveillance. The sensor's ability to sense/trap traces of toxic Cu2+ can provide an early warning about the growing toxicity in a particular resource, thereby providing an opportunity to initiate remediation protocols for speedy decontamination.

A gold speciation that adds a second layer to synergistic gold-copper toxicity in Cupriavidus metallidurans.

The metal-resistant bacterium Cupriavidus metallidurans occurs in metal-rich environments. In auriferous soils, the bacterium is challenged by a mixture of copper ions and gold complexes, which exert synergistic toxicity. The previously used, self-made Au(III) solution caused a synergistic toxicity of copper and gold that was based on the inhibition of the CupA-mediated efflux of cytoplasmic Cu(I) by Au(I) in this cellular compartment. In this publication, the response of the bacterium to gold and copper was investigated by using a commercially available Au(III) solution instead of the self-made solution. The new solution was five times more toxic than the previously used one. Increased toxicity was accompanied by greater accumulation of gold atoms by the cells. The contribution of copper resistance determinants to the commercially available Au(III) solution and synergistic gold-copper toxicity was studied using single- and multiple-deletion mutants. The commercially available Au(III) solution inhibited periplasmic Cu(I) homeostasis, which is required for the allocation of copper ions to copper-dependent proteins in this compartment. The presence of the gene for the periplasmic Cu(I) and Au(I) oxidase, CopA, decreased the cellular copper and gold content. Transcriptional reporter gene fusions showed that up-regulation of gig, encoding a minor contributor to copper resistance, was strictly glutathione dependent. Glutathione was also required to resist synergistic gold-copper toxicity. The new data indicated a second layer of synergistic copper-gold toxicity caused by the commercial Au(III) solution, inhibition of the periplasmic copper homeostasis in addition to the cytoplasmic one.IMPORTANCEWhen living in auriferous soils, Cupriavidus metallidurans is not only confronted with synergistic toxicity of copper ions and gold complexes but also by different gold species. A previously used gold solution made by using aqua regia resulted in the formation of periplasmic gold nanoparticles, and the cells were protected against gold toxicity by the periplasmic Cu(I) and Au(I) oxidase CopA. To understand the role of different gold species in the environment, another Au(III) solution was commercially acquired. This compound was more toxic due to a higher accumulation of gold atoms by the cells and inhibition of periplasmic Cu(I) homeostasis. Thus, the geo-biochemical conditions might influence Au(III) speciation. The resulting Au(III) species may subsequently interact in different ways with C. metallidurans and its copper homeostasis system in the cytoplasm and periplasm. This study reveals that the geochemical conditions may decide whether bacteria are able to form gold nanoparticles or not.

Gene expression profiling of Jack Pine (Pinus banksiana) under copper stress: Identification of genes associated with copper resistance.

Understanding the genetic response of plants to copper stress is a necessary step to improving the utility of plants for environmental remediation and restoration. The objectives of this study were to: 1) characterize the transcriptome of Jack Pine (Pinus banksiana) under copper stress, 2) analyze the gene expression profile shifts of genotypes exposed to copper ion toxicity, and 3) identify genes associated with copper resistance. Pinus banksiana seedlings were treated with 10 mmoles of copper and screened in a growth chamber. There were 6,213 upregulated and 29,038 downregulated genes expressed in the copper resistant genotypes compared to the susceptible genotypes at a high stringency based on the false discovery rate (FDR). Overall, 25,552 transcripts were assigned gene ontology. Among the top upregulated genes, the response to stress, the biosynthetic process, and the response to chemical stimuli terms represented the highest proportion of gene expression for the biological processes. For the molecular function category, the majority of expressed genes were associated with nucleotide binding followed by transporter activity, and kinase activity. The majority of upregulated genes were located in the plasma membrane while half of the total downregulated genes were associated with the extracellular region. Two candidate genes associated with copper resistance were identified including genes encoding for heavy metal-associated isoprenylated plant proteins (AtHIP20 and AtHIP26) and a gene encoding the pleiotropic drug resistance protein 1 (NtPDR1). This study represents the first report of transcriptomic responses of a conifer species to copper ions.

A novel bola-molecular self-assembling hydrogel for enhancing diabetic wound healing

HypothesisChronic wounds, particularly those caused by diabetes, pose a significant challenge for clinical treatment due to their prolonged healing process and associated complications, which can lead to increased morbidity. A biocompatible hydrogel with strong antibacterial properties and the ability to promote angiogenesis can be directly absorbed in the wound site for healing. ExperimentsA series of self-healing, antibacterial bolaamphiphilic supramolecular self-assembling hydrogels (HLQMes/Cu) were developed based on metal–ligand coordination between various concentrations of Cu2+ solution and the head group of l-histidine methyl ester in HLQMes. This is the first report on the application of bola-molecular supramolecular hydrogels for the treatment of chronic wounds. FindingsThe bola-molecular hydrogels reduced the toxicity of copper ions by coordination, and the HLQMes/Cu hydrogel, with 1.3 mg/mL Cu2+ (HLQMes/Cu1.3), demonstrated good biocompatibility and antibacterial properties and effectively enhanced wound healing in a diabetic wound model with full-thickness injuries. Immunohistochemical analysis revealed that the HLQMes/Cu1.3 hydrogel enhanced epithelial formation and collagen deposition in wounds. Immunofluorescence studies confirmed that the HLQMes/Cu1.3 hydrogel attenuated the expression of proinflammatory factor (IL-6) and promoted angiogenesis by upregulating α-SMA and CD31. These findings demonstrate the potential of this bolaamphiphilic supramolecular self-assembling hydrogel as a promising candidate for diabetic wound treatment.

Evaluation the toxic effect of copper ions on the condition indices of benthic diatom Actinocyclus subtilis (W.Gregory) Ralfs 1861 in the experiment

Introduction. Pollution of marine coastal areas lead to the relevance of environmental monitoring including application of biotesting methods based on- the cultures of unicellular algae. Microalgae have different species-specific resistance to pollutants that expands application of different species as bioindicators of marine pollution.
 The aim of the study was to determine the threshold concentration of copper ions (Cu2+) for the survival and increase in the cells number of benthic diatom Actinocyclus subtilis (W.Gregory) Ralfs 1861 (Bacillariophyta) under the wide range of toxicant concentrations during 10-day toxicological experiments.
 Material and methods. The response of strain culture of the benthic diatom A. subtilis to various concentrations of copper sulfate (ranged from 16 to 1024 μg/l in terms of Cu2+ ions) was studied. In accordance with the previously developed protocol, the following indices were evaluated: alterations in the absolute number and proportion (%) of alive cells in the test-culture, as well as the specific growth rate in the number of A. subtilis cells at different concentrations of toxicant. Counting of alive and dead cells was carried out by micrographs taken for 12–15 random viewing fields under Nikon Eclipse inverted light microscope.
 Results. It was found that in the control and at concentration of copper ions 16 μg/l, the increase in the absolute number of cells in culture is described by sigmoid response curve. At the control еhe exponential growth phase occurs on days 5–7 and at concentration of 16 µg/l on days 3–5 of the experiment. The threshold concentration of copper ions (32 μg/l) which is critical for the survival of A. subtilis was determined, which is 3–7 times lower than threshold level for other benthic diatom species. At concentration of 32 µg/l, the phases of acceleration and exponential growth on the abundance curve are absent. The proportion of living cells in the culture decreases to 80% of the control level on day 3 and to 39% by day 10. At Cu2+ concentrations of 64 µg/l and above, sharp inhibition and death of culture is observed as early as 1–3 days. A positive specific growth rate of A. subtilis culture was revealed in the period of 1–5 days at copper concentration of 16 and 
 32 µg/l, and at concentration of 64 µg/l and higher the culture dies off. Negative values of the specific growth rate for all concentrations of the toxicant within the period of 5–10 days were obtained.
 Limitations. By the results of 10-day experiments the effect of 8 concentrations of copper sulfate on the culture of marine benthic diatom A. subtilis was studied. Three replicates in each concentration and exposure time were measured (1350 measurements in total), which is sufficient sampling for statistically reliable determination of the threshold values of copper ion toxicity for given test object.
 Conclusion. Considering the results obtained, the benthic diatom A. subtilis is highly sensitive to copper ions impact and can be recommended as new test-object for toxicology, as well as for application in monitoring of marine water areas subject to technogenic pollution.

Full Copper Resistance in Cupriavidus metallidurans Requires the Interplay of Many Resistance Systems.

The metal-resistant bacterium Cupriavidus metallidurans uses its copper resistance components to survive the synergistic toxicity of copper ions and gold complexes in auriferous soils. The cup, cop, cus, and gig determinants encode as central component the Cu(I)-exporting PIB1-type ATPase CupA, the periplasmic Cu(I)-oxidase CopA, the transenvelope efflux system CusCBA, and the Gig system with unknown function, respectively. The interplay of these systems with each other and with glutathione (GSH) was analyzed. Copper resistance in single and multiple mutants up to the quintuple mutant was characterized in dose-response curves, Live/Dead-staining, and atomic copper and glutathione content of the cells. The regulation of the cus and gig determinants was studied using reporter gene fusions and in case of gig also RT-PCR studies, which verified the operon structure of gigPABT. All five systems contributed to copper resistance in the order of importance: Cup, Cop, Cus, GSH, and Gig. Only Cup was able to increase copper resistance of the Δcop Δcup Δcus Δgig ΔgshA quintuple mutant but the other systems were required to increase copper resistance of the Δcop Δcus Δgig ΔgshA quadruple mutant to the parent level. Removal of the Cop system resulted in a clear decrease of copper resistance in most strain backgrounds. Cus cooperated with and partially substituted Cop. Gig and GSH cooperated with Cop, Cus, and Cup. Copper resistance is thus the result of an interplay of many systems. IMPORTANCE The ability of bacteria to maintain homeostasis of the essential-but-toxic "Janus"-faced element copper is important for their survival in many natural environments but also in case of pathogenic bacteria in their respective host. The most important contributors to copper homeostasis have been identified in the last decades and comprise PIB1-type ATPases, periplasmic copper- and oxygen-dependent copper oxidases, transenvelope efflux systems, and glutathione; however, it is not known how all these players interact. This publication investigates this interplay and describes copper homeostasis as a trait emerging from a network of interacting resistance systems.

Electrocoagulation for the Treatment of Metals Machining Plants Effluents: Experimental and Modeling Study

AbstractTreatment of effluents discharged from mechanical machining of copper and copper alloys for removal of cutting oils and toxic copper ions by electrocoagulation was studied using a cell containing two steel electrodes and a built‐in heat transfer facility. Current density, initial pH of the solution, temperature, starting pollutants' concentrations, amount of NaCl supportive electrolyte, and the impact of gas sparging were investigated. Response surface methodology was used to correlate % oil removal, % copper removal, and electrical energy consumption to the affecting variables. The results imply that the cubic model fits well with the experimental results. The electrocoagulation of oil and copper from waste solutions was optimized using the response optimizer. The simultaneous removal of oil and Cu2+ in the same cell could lower the operational and capital expenses of wastewater treatment.

Novel Fe–Mn oxide/zeolite composite material for rapid removal of toxic copper ions from aqueous solutions

In this study, Fe–Mn oxide/zeolite composites were synthesized through the coprecipitation and utilized as an adsorbent for the removal of copper ions from aqueous solution. The physico-chemical properties of the adsorbent were disclosed by X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscopy, automatic micropore analyzer, and surface potential (Zeta) investigation, demonstrating the successful synthesis of the adsorbent. The abundant negative charge and hydroxyl functional group as well as pore structure on the adsorbent surface were very conducive to the removal of copper ions. The effects of adsorbent dosage, the initial concentration of copper ions, the initial pH, and the contact time on adsorption were investigated in batch adsorption experiments. The adsorption followed the pseudo-second-order kinetic model and Langmuir isothermal theory，which showed that the adsorption process was monolayer chemisorption. The complexation reaction of functional groups that contain oxygen, electrostatic attraction, precipitation, and physical adsorption are the primary components of the removal of copper ions mechanism. The results showed that when pH = 6, the leaching concentration of iron and manganese was lower than 0.1 mg/L. In addition, after five cycles of test, the adsorbent could still guarantee 88% of the previous adsorption capacity. The adsorbent exhibits exceptional stability, which is crucial for its use in real water bodies. Thus, this research offered a handy strategy for copper ions removal from aqueous solution.

Effects of surface-functionalized TiO2nanoparticles on copper ion toxicity under simultaneous and sequential exposure conditions

The toxicity of nano-TiO2and Cu2+should consider both the nature of nano-TiO2and the exposure scenarios.

Copper mining bacteria: Converting toxic copper ions into a stable single-atom copper.

The chemical synthesis of monoatomic metallic copper is unfavorable and requires inert or reductive conditions and the use of toxic reagents. Here, we report the environmental extraction and conversion of CuSO4 ions into single-atom zero-valent copper (Cu0) by a copper-resistant bacterium isolated from a copper mine in Brazil. Furthermore, the biosynthetic mechanism of Cu0 production is proposed via proteomics analysis. This microbial conversion is carried out naturally under aerobic conditions eliminating toxic solvents. One of the most advanced commercially available transmission electron microscopy systems on the market (NeoArm) was used to demonstrate the abundant intracellular synthesis of single-atom zero-valent copper by this bacterium. This finding shows that microbes in acid mine drainages can naturally extract metal ions, such as copper, and transform them into a valuable commodity.

A metal-organic-framework incorporated vascular graft for sustained nitric oxide generation and long-term vascular patency

Copper-MOFs (Cu-MOFs) have been reported to demonstrate great potential as cardiovascular biomaterials, due to enhanced catalytic ability of Cu2+ to generate nitric oxide (NO) from endogenous S-nitrosothiols (RSNOs). However, free Cu-MOFs usually show rapid degradation under physiological conditions, resulting in short catalytic half-life and risk of copper ion toxicity. Therefore, how to increase the stability of Cu-MOFs is of great importance in cardiovascular biomaterials research. Herein, we chose M199 MOF as an example and developed Cu-MOF-based scaffold, using the electrospinning method to embed Cu-MOF nanoparticles into polycaprolactone (PCL) fibers. Entrapment of Cu-MOF nanoparticles within PCL could simultaneously enhance Cu-MOF stability in serum and allow for long-term NO catalytic activity, as assessed by in vitro assays and using in situ implantation models. Additionally, the optimized concentration of Cu-MOFs loaded within the scaffolds significantly promoted endothelial cell (EC) migration and increased acetylated low-density lipoprotein (Ac-LDL) uptake. Moreover, Cu-MOF-based scaffolds dramatically inhibited platelet adhesion and activation, which markedly reduced acute thrombosis in arterio-venous shunt models. In situ implantation experiments revealed that the PCL/Cu-MOF scaffolds accelerated the formation of an intact endothelial monolayer. Together, these results suggest that the incorporation of Cu-MOFs into electrospun fibers could serve as a promising approach to achieve stable catalytic performance and long-term activity required for implant materials.

Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer

Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic KRAS has been extremely challenging to target therapeutically. To identify potential vulnerabilities in KRAS-mutated CRC, we characterize the impact of oncogenic KRAS on the cell surface of intestinal epithelial cells. Here we show that oncogenic KRAS alters the expression of a myriad of cell-surface proteins implicated in diverse biological functions, and identify many potential surface-accessible therapeutic targets. Cell surface-based loss-of-function screens reveal that ATP7A, a copper-exporter upregulated by mutant KRAS, is essential for neoplastic growth. ATP7A is upregulated at the surface of KRAS-mutated CRC, and protects cells from excess copper-ion toxicity. We find that KRAS-mutated cells acquire copper via a non-canonical mechanism involving macropinocytosis, which appears to be required to support their growth. Together, these results indicate that copper bioavailability is a KRAS-selective vulnerability that could be exploited for the treatment of KRAS-mutated neoplasms.

Rainbow trout (Oncorhynchus mykiss) chemosensory detection of and reactions to copper nanoparticles and copper ions

Copper is known to interfere with fish olfaction. Although the chemosensory detection and olfactory toxicity of copper ions (Cu2+) has been heavily studied in fish, the olfactory-driven detection of copper nanoparticles (CuNPs)—a rapidly emerging contaminant to aquatic systems—remains largely unknown. This study aimed to investigate the olfactory response of rainbow trout to equitoxic concentrations of CuNPs or Cu2+ using electro-olfactography (EOG, a neurophysiological technique) and olfactory-mediated behavioural assay. In the first experiment, the concentration of contaminants known to impair olfaction by 20% over 24 h (EOG-based 24-h IC20s of 220 and 3.5 μg/L for CuNPs and Cu2+, respectively) were tested as olfactory stimuli using both neurophysiological and behavioural assays. In the second experiment, to determine whether the presence of CuNPs or Cu2+ can affect the ability of fish to perceive a social cue (taurocholic acid (TCA)), fish were acutely exposed to one form of Cu-contaminants (approximately 15 min). Following exposure, olfactory sensitivity was measured by EOG and olfactory-mediated behaviour within a choice maze was recorded in the presence of TCA. Results of neurophysiological and behavioural experiments demonstrate that rainbow trout can detect and avoid the IC20 of CuNPs. The IC20 of Cu2+ was below the olfactory detection threshold of rainbow trout, as such, fish did not avoid Cu2+. The high sensitivity of behavioural endpoints revealed a lack of aversion response to TCA in CuNP-exposed fish, despite this change not being present utilizing EOG. The reduced response to TCA during the brief exposure to CuNPs may be a result of either olfactory fatigue or blockage of olfactory sensory neurons (OSNs) by CuNPs. The observed behavioural interference caused by CuNP exposure may indicate that CuNPs have the ability to interfere with other behaviours potentially affecting fitness and survival. Our findings also revealed the differential response of OSNs to CuNPs and Cu2+.

Superhydrophobic copper in biological liquids: Antibacterial activity and microbiologically induced or inhibited corrosion

The bactericidal activity of copper and copper alloys is well appreciated and was already exploited in medical practice in 19th century. However, despite of being an essential nutrient required by organisms to perform life functions, excess copper is extremely toxic and detrimental to health. Recent studies have shown that superhydrophobic surfaces have a significant antibacterial potential for reduction of nosocomial infections. At the same time, the prolonged contact with biological liquids may cause a degradation of the superhydrophobic copper surface and corrosion with increasing egress of toxic copper ions. These aspects are poorly studied so far. In this paper, we analyze the evolution of the properties of both the superhydrophobic copper surface and the suspension of Escherichia coli bacteria during their prolonged contact and study the impact of such contact on the bactericidal activity of the surface. It is shown that by controlling the corrosion resistance and the wettability of the superhydrophobic copper substrate, it becomes possible to sustain the bactericidal action of copper substrates for a long time, simultaneously avoiding the excessive corrosive degradation and release of copper ions in the environment.

Silver Ions as a Tool for Understanding Different Aspects of Copper Metabolism.

In humans, copper is an important micronutrient because it is a cofactor of ubiquitous and brain-specific cuproenzymes, as well as a secondary messenger. Failure of the mechanisms supporting copper balance leads to the development of neurodegenerative, oncological, and other severe disorders, whose treatment requires a detailed understanding of copper metabolism. In the body, bioavailable copper exists in two stable oxidation states, Cu(I) and Cu(II), both of which are highly toxic. The toxicity of copper ions is usually overcome by coordinating them with a wide range of ligands. These include the active cuproenzyme centers, copper-binding protein motifs to ensure the safe delivery of copper to its physiological location, and participants in the Cu(I) ↔ Cu(II) redox cycle, in which cellular copper is stored. The use of modern experimental approaches has allowed the overall picture of copper turnover in the cells and the organism to be clarified. However, many aspects of this process remain poorly understood. Some of them can be found out using abiogenic silver ions (Ag(I)), which are isoelectronic to Cu(I). This review covers the physicochemical principles of the ability of Ag(I) to substitute for copper ions in transport proteins and cuproenzyme active sites, the effectiveness of using Ag(I) to study copper routes in the cells and the body, and the limitations associated with Ag(I) remaining stable in only one oxidation state. The use of Ag(I) to restrict copper transport to tumors and the consequences of large-scale use of silver nanoparticles for human health are also discussed.

Antimicrobial properties of Cu-based bulk metallic glass composites after surface modification

The aim of this work is to study the influence of two surface modification methods, surface grinding to change the surface roughness (from 240 to 4000 grit) and oxidation (furnace at 703 K for 5 h in air), on antibacterial activity against E. coli K12 of a Cu-based bulk metallic glass composite (BMGC). Variations of roughness obtained through grinding in both as-cast and oxidized samples had a minimal effect on antimicrobial activity. Oxidation in resulted in a multilayered structure with an outer CuO layer, followed by Cu2O layer and other phases at greater depths according to microscopy and energy dispersive X-ray results. This oxidation increased antimicrobial performance despite the CuO layer is poorer in copper than the Cu55Zr40Al5 at. % bulk metallic glass composite substrate. This improvement could be attributed to microstructural differences between the layer and the substrate. The fine needle-shape structure of the crystalline oxide layer may account for the improvement since interphase boundaries could constitute easy diffusion paths for Cu ion release while the shape could trigger mechanosensitive channels that can favour and thus promote the migration of copper ions into the cell. Microscopy of the deposited bacteria revealed limited changes of the outer layer of the cells, with slight changes in morphology for the oxidized samples and this is attributed to the higher copper ion released. Minimum Inhibitory Concentration tests revealed that cell degradation takes place at copper concentrations of 222.4 mg/mL, much higher than measurements of copper ion diffusion in the as-cast samples, suggesting that lysis is not the first step in copper ion toxicity. These studies indicate that Cu55Zr40Al5 bulk metallic glass composite shows promise as an antimicrobial material with tuned performance through surface oxidation.

The Role of High Voltage Electrode Material in the Inactivation of E. coli by Direct-in-Liquid Electrical Discharge Plasma

This work investigates the effect of high voltage (HV) electrode material of a point-plane plasma reactor on the inactivation rate of E. coli in both direct plasma and post-discharge inactivation processes. For the direct plasma processes, nickel chromium alloy, iron, tungsten and copper were used as HV electrode materials. In comparison with the other three materials, a significantly higher inactivation rate of E. coli was achieved with copper as the HV electrode. The inactivation effect was demonstrated to be mainly associated with the toxicity of copper ions, rather than from copper nanoparticles released from the electrode during the treatment. Similarly, for the post-discharge inactivation process, a higher E. coli inactivation rate was achieved in both post-plasma and plasma-treated water treatment using copper as the HV electrode, as compared to the tungsten control case. Increased inactivation rates are a result of a synergistic action between copper ions and the hydrogen peroxide generated by the plasma.

Sublethal doses of copper sulphate initiate deregulation of glial cytoskeleton, NF-kB and PARP expression in Capoeta umbla brain tissue

Copper sulphate pentahydrate (CuSO4∙5H2O) is widely used as a pesticide not only in agricultural but in aquaculture farming as well. Copper sulphate is a cheap chemical and able to contaminate the environment, especially water sources, which is crucial for fish harvesting and farming. The copper contamination in some areas is caused over decades because this pesticide has long been used everywhere. Copper ions inhibit invasive aquatic plants and many microorganisms but contaminate soil and natural water resources. The family of copper-containing chemicals is frequently used as algaecides in swimming pools. Despite the high toxicity of copper ions for fish in freshwater ponds, copper sulphate remains one of the prevalent pesticides in fish farming everywhere. High cytotoxicity and accumulation of the copper ions in sediments require study and calculation of the optimal dosage for its use as an antiseptic agent which will not have a detrimental effect on various tissue types of aquatic organisms. The main recognized mechanism which accompanies the toxic effect of copper ions is the generation of oxidative stress. Neural tissue cells are extremely susceptible to oxidative damage and the functions of the CNS are critical to the vitality of organisms. Glial cells maintain the structure and many vital functions of neurons. The cytoskeleton glial fibrillary acidic protein (GFAP), transcriptional nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and Poly(ADP-ribose) polymerase (PARP) are critical participants in a cellular response to a toxic agent impact. As this takes place, it could be applied in biomarking of heavy metal toxicity. In the presented study, we investigated the effects of copper ions on PARP, NF-kB, and GFAP expression in the Tigris scraper Capoeta umbla brain tissue. For 96 hours the fish were exposed to copper sulphate at sublethal concentrations, namely 1/2, 1/4 and 1/8 of the LD50 value. Western blot analysis of GFAP and PARP was used to assess further effects in the brain tissue. Every studied dose of copper significantly downregulated the expression of GFAP after 72 hours of treatment. In spite of the common increment in the GFAP content, 48 hours exposure to copper initiated the upregulation of that cytoskeleton marker. Moreover, treatment with copper sulphate induced several changes in the β-actin level, especially in the fish group treated for 72 hours. The observed effect of copper in the fish brain evidences the unspecific toxic effect of the copper ions in the brain tissue cells. The obtained results demonstrated meaningful disturbance in the expression of transcriptional factor NF-kB in the brain of the fish group exposed to copper. The changes found in the fish brain indicate the dose-dependent effect in a concentration range 185–740 µg/L of copper sulphate during 72 hours. However, the exposure to low dose of copper ions showed no effect in the fish group treated for 24 hours. Comparative analyses of the PARP content in the brain of fish exposed to copper for 72 hours was significantly less than in the groups treated with copper for both 24 and 48 hours. Thus, the copper ions in the dose range 185–740 µg/L can suppress PARP expression in a time-dependent manner. The results showed that copper ions could induce astroglial response accompanied by modulations of NF-kB and PARP-1 expression. The data obtained in this study suggest that copper sulphate has a significant effect on astrogliosis and DNA damage in the fish brain.

Nitration of amyloid-β peptide (1–42) as a protective mechanism for the amyloid-β peptide (1–42) against copper ion toxicity

It is known that copper ion (Cu(II)) binds to amyloid-β peptide (Aβ), induces Aβ oligomer formation and ultimately exacerbates Aβ-aggregation neurotoxicity in Alzheimer's disease (AD). It becomes interesting to know that how this chemical modification of Aβ would affect interaction of Aβ and Cu(II) and their roles in the development of AD. In this work, we investigated the interaction of Aβ1–42 nitration with the toxic Cu(II). It showed that Cu(II)induced Aβ1–42 nitration in the presence of nitrite and hydrogen peroxide. Circular dichroism studies also revealed significant conformational change of Aβ1–42 and Tyr10 nitrated amyloid-β peptide(1–42) (Aβ1–42NT) when interacting with Cu(II). Even though nitration did not alter the binding of Aβ1–42 to Cu(II) or the peroxidative activity of Aβ1–42-Cu(II) complex, nitration ameliorated the aggregation and neurotoxicity of Aβ1–42 induced by Cu(II), which was also further confirmed by the cell study. Given our previous findings that Aβ nitration dramatically inhibited its aggregation and thus reduced its toxicity, we speculated that nitration of Aβ1–42 altered its intermolecular interaction, which protected itself against the toxicity of Cu(II). Based on this hypothesis, we propose that nitration of Aβ1–42 may be an important protective mechanism for normal function of Aβ1–42 and deserves more attention in AD drug development.