Acclimation to Low Level Exposure of Copper in Bufo arenarum Embryos: Linkage of Effects to Tissue Residues

PubMed Central

Herkovits, Jorge; Pérez-Coll, Cristina Silvia

2007-01-01

The acclimation possibilities to copper in Bufo arenarum embryos was evaluated by means of three different low level copper exposure conditions during 14 days. By the end of the acclimation period the copper content in control embryos was 1.04 ± 0.09 μg.g−1 (wet weight) while in all the acclimated embryos a reduction of about 25% of copper was found. Thus copper content could be considered as a biomarker of low level exposure conditions. Batches of 10 embryos (by triplicate) from each acclimation condition were challenged with three different toxic concentrations of copper. As a general pattern, the acclimation protocol to copper exerted a transient beneficial effect on the survival of the Bufo arenarum embryos. The acclimation phenomenon could be related to the selection of pollution tolerant organisms within an adaptive process and therefore the persistence of information within an ecological system following a toxicological stressor. PMID:17617681

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit

PubMed Central

LAMB, DAVID J; AVADES, TONY Y; FERNS, GORDON AA

2001-01-01

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25–1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 ± 0.78 vs. 1.33 ± 0.46 µg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 ± 21 IU/mg tissue) compared to the other groups (187 ± 21; 239 ± 53; 201 ± 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 ± 5.5%) and a deficient diet (0 mg/day) (63.1 ± 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 ± 6.3 and 42.8 ± 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population. PMID:11703538

Impact of ionophore monensin on performance and Cu uptake in earthworm Eisenia andrei exposed to copper-contaminated soil.

PubMed

Zidar, Primož; Kos, Monika; Vogel-Mikuš, Katarina; van Elteren, Johannes Teun; Debeljak, Marta; Žižek, Suzana

2016-10-01

Exposure of beneficial soil organisms to chemical mixtures is of great concern and can result in unexpected deleterious consequences. We investigated the effects of concurrent soil contamination with monensin, a veterinary pharmaceutical and feed additive, and copper, on earthworm copper uptake and reproductive success. The animals were exposed for 14 or 28 days to both substances and the results showed that the Cu body burden of earthworms increases in the presence of monensin. The harmful effects of Cu on earthworm cocoon production were considerably higher when monensin was also present in the soil. To localise the copper in earthworm tissues, histological staining was performed using two different dyes (rubeanic acid and 5-4-(p-dimethylaminobenzylidene)-rhodanine). Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to quantify the Cu levels in the tissues. Cu was found predominantly in the gut wall. The Cu content in the body wall was at least ten times lower compared to the gut, but was proportional to the level of soil contamination. Concurrent soil contamination with monensin and copper resulted in higher earthworm Cu levels and in decreased reproductive success of these important soil decomposers. Copyright © 2016 Elsevier Ltd. All rights reserved.

NA{sup +}, K{sup +}-ATPase, histopathological, and genetic responses of Corbicula fluminea to sediment-associated copper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, S.

1995-12-31

Time-dependent responses to sediment-associated copper were studies at hierarchical levels of biological organization along an extreme concentration gradient (40 to 40,000 mg/kg total Cu). Laboratory and in situ estimates of molecular to tissue-level responses (Na/K-ATPase activity, DNA content, histopathology) were monitored in Corbicula fluminea (Asiatic clam), and compared with laboratory and field based survival of Corbicula and Elimia teres (an indigenous Gastropoda). Mollusc survival was, in turn, compared with effects on macrobenthic community composition along the stream/[Cu] gradient. Relationships between selected sediment characteristics and the bioavailability and toxicity of sediment associated copper were also investigated. Sediment-associated copper depressed Na/K-ATPase activitymore » and led to histopathological damage of renal and gill epithelia (vacuolization, degeneration), indicating that impaired ion regulation was an important mechanism of toxicity. Concurrent reductions in DNA content were believed to be secondary effects due to cell death, not an indication of genotoxicity. Sublethal responses were significantly correlated with survival in both species; however, while survival in situ was indicative of differences in community structure, laboratory-based survival was not. Copper levels in tissues were indicative of exposure, but were not significantly correlated with adverse effects. Copper levels in sediments, interstitial water, and overlying water varied independently of sediment characteristics except pH. Cu/AVS ratios were predictive of Corbicula and Elimia survival, but were not significantly related to differences in community structure. Instead, macrobenthic community structure was influenced by other sediment factors (grain size, Eh, pH).« less

Characterization of the yeast copper-inducible promoter system in Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Granger, C. L.; Cyr, R. J.

2001-01-01

Inducible promoters or gene-switches are used to both spatially and temporally regulate gene expression. Such regulation can provide information concerning the function of a gene in a developmental context as well as avoid potential harmful effects due to overexpression. A gfp construct under the control of a copper-inducible promoter was introduced into Arabidopsis thaliana (L.) Heynh. and the regulatory parameters of this inducible promoter were determined. Here, we describe the time-course of up- and down-regulation of GFP expression in response to copper level, the optimal regulatory levels of copper, and the tissue specificity of expression in three transgenic lines. We conclude that the copper-inducible promoter system may be useful in regulating the time and location of gene expression in A. thaliana.

Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

PubMed

Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed

2012-10-01

Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Correlation of Lethal Concentrations of Heavy Metals with Tissue Levels of Earthworms

DTIC Science & Technology

1988-08-01

mentioned in the contract i.e. mercury , arsenic, ’cadmium and copper. We will find out the 50 % lethal concentrations (LC50) and the smallest...concentrations, blanks, and background worm stock has been limited to copper and cadmium. In fact, mercury and arsenic request special analytical device...the other boxes but without toxic components. Contaminants to study are heavy metals : cadmium, copper and mercury , and arsenic. We chose following

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

PubMed

Wang, F; Jiao, P; Qi, M; Frezza, M; Dou, Q P; Yan, B

2010-01-01

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes.

PubMed

Wei, Xiang-Bo; Guo, Liang; Liu, Yang; Zhou, Shui-Rong; Liu, Yuan; Dou, Xin; Du, Shao-Yue; Ding, Meng; Peng, Wan-Qiu; Qian, Shu-Wen; Huang, Hai-Yan; Tang, Qi-Qun

2017-09-23

Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM. Copyright © 2017. Published by Elsevier Inc.

Using XAS and SXRF to Study Copper in Wilson Disease at the Molecular and Tissue Level

NASA Astrophysics Data System (ADS)

Ralle, Martina; Blackburn, Ninian J.; Lutsenko, Svetlana

2007-02-01

Wilson disease (WD) is a genetic disorder of copper metabolism associated with severe hepatic, neurological, and psychiatric abnormalities. In WD, the billiary copper excretion is impaired and copper accumulates in tissues, particularly in the liver and the brain. The affected gene, ATP7B, encodes the copper transporting ATPase, Wilson disease protein (WNDP). WNDP has six copper binding sites in the N-terminal portion of the molecule. Each site includes the conserved amino acid sequence MXCXXC, and binds 1 Cu(I) through its 2 cysteine residues. We performed X-ray absorption studies at the Cu Kα-edge on the recombinant N-terminal domain of WNDP (N-WNDP). Copper was bound to N-WNDP either in vivo or in vitro in the presence of different reducing agents. We found that in N-WNDP copper is predominantly coordinated in a linear fashion by two cysteines, with the appearance of a Cu-Cu interaction when all metal binding sites are filled. Increasing amounts of reducing agents containing sulfide or phosphine groups led to binding of the exogenous ligands to copper thereby increasing the coordination number of copper from two to three. To better understand the role of copper in WD, we utilized livers of the 6-weeks-old Atp7b-/- mice (an animal model for WD) in which the copper concentration was 10-20-fold higher compared to that of the control mice. The distribution of copper in hepatocytes was evaluated by synchrotron based X-ray fluorescence microprobe (SXRF). We demonstrate that we can prepare liver slices that retain copper and can detect copper with subcellular resolution. On the same sections μ-XANES (spot size: 5 micron) was used to determine the oxidation state of copper.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution.

PubMed

Denoyer, Delphine; Pearson, Helen B; Clatworthy, Sharnel A S; Smith, Zoe M; Francis, Paul S; Llanos, Roxana M; Volitakis, Irene; Phillips, Wayne A; Meggyesy, Peter M; Masaldan, Shashank; Cater, Michael A

2016-06-14

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

PubMed Central

Denoyer, Delphine; Pearson, Helen B.; Clatworthy, Sharnel A.S.; Smith, Zoe M.; Francis, Paul S.; Llanos, Roxana M.; Volitakis, Irene; Phillips, Wayne A.; Meggyesy, Peter M.; Masaldan, Shashank; Cater, Michael A.

2016-01-01

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed. PMID:27175597

The Role of Trace Elements in Tinnitus.

PubMed

Yaşar, Mehmet; Şahin, Mehmet İlhan; Karakükçü, Çiğdem; Güneri, Erhan; Doğan, Murat; Sağıt, Mustafa

2017-03-01

In this study, we aimed to investigate the role of three trace elements, namely, zinc, copper, and lead, in tinnitus by analyzing the serum level of copper and lead and both the serum and tissue level of zinc. Eighty patients, who applied to outpatient otolaryngology clinic with the complaints of having tinnitus, and 28 healthy volunteers were included. High-frequency audiometry was performed, and participants who had hearing loss according to the pure tone average were excluded; tinnitus frequency and loudness were determined and tinnitus reaction questionnaire scores were obtained from the patients. Of all the participants, serum zinc, copper, and lead values were measured; moreover, zinc levels were examined in hair samples. The levels of trace elements were compared between tinnitus and control groups. The level of copper was found to be significantly lower in the tinnitus group (p = 0.02), but there was no significant difference between the groups in terms of the levels of zinc, neither in serum nor in hair, and lead in serum (p > 0.05). The lack of trace elements, especially that of "zinc," have been doubted for the etiopathogenesis of tinnitus in the literature; however, we only found copper levels to be low in patients having tinnitus.

Cardiac catecholamines in rats fed copper deficient or copper adequate diets containing fructose or starch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scholfield, D.J.; Fields, M.; Beal, T.

1989-02-09

The symptoms of copper (Cu) deficiency are known to be more severe when rats are fed a diet with fructose (F) as the principal carbohydrate. Mortality, in males, due to cardiac abnormalities usually occurs after five weeks of a 62% F, 0.6 ppm Cu deficient diet. These effects are not observed if cornstarch (CS) is the carbohydrate (CHO) source. Studies with F containing diets have shown increased catecholamine (C) turnover rates while diets deficient in Cu result in decreased norepinephrine (N) levels in tissues. Dopamine B-hydroxylase (EC 1.14.17.1) is a Cu dependent enzyme which catalyzes the conversion of dopamine (D)more » to N. An experiment was designed to investigate the effects of CHO and dietary Cu on levels of three C in cardiac tissue. Thirty-two male and female Sprague-Dawley rats were fed Cu deficient or adequate diets with 60% of calories from F or CS for 6 weeks. N, epinephrine (E) and D were measured by HPLC. Statistical analysis indicates that Cu deficiency tends to decrease N levels, while having the reverse effect on E. D did not appear to change. These findings indicate that Cu deficiency but not dietary CHO can affect the concentration of N and E in rat cardiac tissue.« less

Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism.

PubMed

Khan, Husain Y; Zubair, Haseeb; Ullah, Mohd F; Ahmad, Aamir; Hadi, Sheikh M

2011-12-01

To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

The cardiac copper chaperone proteins Sco1 and CCS are up-regulated, but Cox 1 and Cox4 are down-regulated, by copper deficiency.

PubMed

Getz, Jean; Lin, Dingbo; Medeiros, Denis M

2011-10-01

Copper is ferried in a cell complexed to chaperone proteins, and in the heart much copper is required for cytochrome c oxidase (Cox). It is not completely understood how copper status affects the levels of these proteins. Here we determined if dietary copper deficiency could up- or down-regulate select copper chaperone proteins and Cox subunits 1 and 4 in cardiac tissue of rats. Sixteen weanling male Long-Evans rats were randomized into treatment groups, one group receiving a copper-deficient diet (<1 mg Cu/kg diet) and one group receiving a diet containing adequate copper (6 mg Cu/kg diet) for 5 weeks. Hearts were removed, weighed, and non-myofibrillar proteins separated to analyze for levels of CCS, Sco1, Ctr1, Cox17, Cox1, and Cox4 by SDS-PAGE and Western blotting. No changes were observed in the concentrations of CTR1 and Cox17 between copper-adequate and copper-deficient rats. CCS and Sco1 were up-regulated and Cox1 and Cox4 were both down-regulated as a result of copper deficiency. These data suggest that select chaperone proteins and may be up-regulated, and Cox1 and 4 down-regulated, by a dietary copper deficiency, whereas others appear not to be affected by copper status.

Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.

PubMed

Goez, Helly R; Jacob, Francois D; Yager, Jerome Y

2011-02-01

Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

Role of Copper and Homocysteine in Pressure Overload Heart Failure

PubMed Central

Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

2009-01-01

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

PubMed Central

Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

2011-01-01

Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

Validating the use of embryonic fish otoliths as recorders of sublethal exposure to copper in estuarine sediments.

PubMed

Barbee, Nicole C; Greig, Alan; Swearer, Stephen E

2013-07-01

In this study we explore the use of fish otoliths ('earbones') as a tool for detecting exposure to heavy metals in sediments. Because otoliths are metabolically inert and incorporate chemical impurities during growth, they can potentially provide a more permanent record of pollutant exposure history in aquatic environments than soft tissues. To validate this technique we cultured embryos of a native Australian fish, the common Galaxias (Galaxias maculatus), in the laboratory on sediments spiked with copper in a concentration gradient. Our aims were to test whether exposure to copper contaminated sediments is recorded in the otoliths of embryos and determine over what range in concentrations we can detect differences in exposure. We found elevated copper levels in otoliths of embryos exposed to high copper concentrations in sediments, suggesting that otoliths can be used as a tool to track a history of exposure to elevated copper levels in the environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans*♦

PubMed Central

Chun, Haarin; Sharma, Anuj Kumar; Lee, Jaekwon; Chan, Jefferson; Jia, Shang; Kim, Byung-Eun

2017-01-01

Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans. Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways. PMID:27881675

Effects of Dietary Copper and Zinc Supplementation on Growth Performance, Tissue Mineral Retention, Antioxidant Status, and Fur Quality in Growing-Furring Blue Foxes (Alopex lagopus).

PubMed

Liu, Zhi; Wu, Xuezhuang; Zhang, Tietao; Guo, Jungang; Gao, Xiuhua; Yang, Fuhe; Xing, Xiumei

2015-12-01

A 4×2 factorial experiment with four supplemental levels of copper (0, 20, 40, or 60 mg copper per kg dry matter) from copper sulfate and two supplemental levels of zinc (40 or 200 mg zinc per kg dry matter) from zinc sulfate was conducted to investigate the effects of dietary copper and zinc supplementation on growth performance, tissue mineral retention, antioxidant status, and fur quality in growing-furring blue foxes. One hundred and twenty healthy 15-week-old male blue foxes were randomly allocated to eight dietary treatments with 15 replicates per treatment for a 70-day trial from mid-September to pelting in December. The average daily gain and feed conversion ratio were increased with copper supplementation in the first 35 days as well as the overall period (P<0.05). In addition, copper supplementation tended to increase feed intake during the first 35 days (P<0.10). Diets supplemented with 200 mg/kg zinc did not affect body gain (P>0.10) and feed intake (P>0.10) but improved feed conversion (P<0.05) compared with those supplemented 40 mg/kg zinc throughout the experiment. No copper×zinc interaction was observed for growth performance except that a tendency (P=0.09) was found for feed intake in the first 35 days. Supplementation of copper or zinc improved crude fat digestibility (P<0.01) but had no effects on the digestibility of other nutrients. Fecal copper was increased with both copper (P<0.01) and zinc addition (P<0.05). However, fecal zinc was affected only by dietary zinc addition (P<0.01). Mineral contents in serum and kidney were not affected by dietary treatments (P>0.05). However, the level of copper in the liver was increased with copper supplementation (P<0.05) and tended to decrease with zinc supplementation (P=0.08). Dietary zinc addition tended to increase the activity of alkaline phosphatase (P=0.07). The activities of copper-zinc superoxide dismutase and catalase tended to increase by copper (P=0.08) and zinc addition (P=0.05). Moreover, a copper×zinc interaction was observed for catalase in the experiment (P<0.05). Serum malondialdehyde concentration decreased with the increasing of dietary copper and zinc levels (P<0.05). The activity of glutathione peroxidase tended to increase by copper addition (P=0.09). For fur quality, foxes fed diets supplemented with high copper had larger skin length and darker pelts than those fed the basal diet without copper addition (P<0.05). In conclusion, this study demonstrated that dietary copper and zinc supplementation can improve growth by increasing feed intake and improving fat digestibility. Additionally, copper and zinc can enhance the antioxidant capacity of blue foxes. This study also indicates that additional zinc up to 200 mg/kg did not exert significant adverse effects on the copper metabolism of growing-furring blue foxes.

Effects of an aged copper contamination on distribution of earthworms, reproduction and cocoon hatchability.

PubMed

Mirmonsef, Hassan; Hornum, Hanne D; Jensen, John; Holmstrup, Martin

2017-01-01

Contaminated soil is a problem throughout the industrialized world, and a significant proportion of these sites are polluted with heavy metals such as copper. Ecological risk assessment of contaminated sites requires ecotoxicological studies with spiked soils as well as in-situ ecological observations. Here, we report laboratory and field assessment of copper toxicity for earthworms at a Danish site (Hygum) exclusively contaminated with an increasing gradient in copper from background to highly toxic levels (>1000mgkg -1 dry soil). More specifically, we report effects on field populations, body contents of copper, hatching of earthworm cocoons and reproduction of the common species Aporrectodea tuberculata. Abundance of earthworms and cocoons decreased significantly from about 400-150m -2 along the gradient as the soil copper concentration increased from ca. 50 to ca. 1000mgkg -1 . At lower concentrations, the population was dominated by endogeic species, whereas at high concentrations the population was dominated by epigeic species. At high copper contents the internal concentration of copper was in the range 100-160mgkg -1 dry tissue. Despite the high internal copper contents, hatchability of field collected cocoons was not impaired in any species. The EC50 reproduction value of A. tuberculata was about 220mg copper kg -1 dry soil in the first two exposure periods, but nearly doubled in the third period suggesting that an acclimation response had occurred. Also in the laboratory reproduction test, cocoon hatchability was not reduced, but rather slightly stimulated by copper. Based on these results we discuss the possibility that acute exposure in laboratory experiments is more detrimental than exposure in a field situation, perhaps because increased tolerance may be acquired through natural selection and genetic adaptation through increased use of defense mechanisms such as metallothioneins. Further, we discuss that the rather high tissue copper level of earthworms from the Hygum site may have smaller effects in these free-ranging worms than it would have in acute-exposure laboratory tests because the copper is more efficiently sequestered and detoxified in the field situation where populations have been exposed for many generations. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary copper in excess of nutritional requirement reduces plasma and breast muscle cholesterol of chickens.

PubMed

Bakalli, R I; Pesti, G M; Ragland, W L; Konjufca, V

1995-02-01

Male commercial broiler strain chickens were fed from hatching to 42 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle cholesterol (20.4% reduction) were observed in copper-supplemented birds. There was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels were very low (< .5 mg/kg). Feeding copper for 42 vs 35 d resulted in lower levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2% reduction). Very similar results were found in two additional experiments in which hypocholesterolemia and reduced breast muscle cholesterol were associated with reduced plasma triglycerides and blood reduced glutathione. It is well known that hypercholesterolemia is a symptom of dietary copper deficiency. The data presented here indicate that blood and breast muscle cholesterol are inversely related to dietary copper in excess of the dietary requirement for maximal growth. The cholesterol content of the edible muscle tissue of broiler chickens can be reduced by approximately 25% after feeding a supranormal level of copper for 42 d without altering the growth of the chickens or substantially increasing the copper content of the edible meat.

The response of Isidorella newcombi to copper exposure: Using an integrated biological framework to interpret transcriptomic responses from RNA-seq analysis.

PubMed

Ubrihien, Rodney P; Ezaz, Tariq; Taylor, Anne M; Stevens, Mark M; Krikowa, Frank; Foster, Simon; Maher, William A

2017-04-01

This study describes the transcriptomic response of the Australian endemic freshwater gastropod Isidorella newcombi exposed to 80±1μg/L of copper for 3days. Analysis of copper tissue concentration, lysosomal membrane destabilisation and RNA-seq were conducted. Copper tissue concentrations confirmed that copper was bioaccumulated by the snails. Increased lysosomal membrane destabilisation in the copper-exposed snails indicated that the snails were stressed as a result of the exposure. Both copper tissue concentrations and lysosomal destabilisation were significantly greater in snails exposed to copper. In order to interpret the RNA-seq data from an ecotoxicological perspective an integrated biological response model was developed that grouped transcriptomic responses into those associated with copper transport and storage, survival mechanisms and cell death. A conceptual model of expected transcriptomic changes resulting from the copper exposure was developed as a basis to assess transcriptomic responses. Transcriptomic changes were evident at all the three levels of the integrated biological response model. Despite lacking statistical significance, increased expression of the gene encoding copper transporting ATPase provided an indication of increased internal transport of copper. Increased expression of genes associated with endocytosis are associated with increased transport of copper to the lysosome for storage in a detoxified form. Survival mechanisms included metabolic depression and processes associated with cellular repair and recycling. There was transcriptomic evidence of increased cell death by apoptosis in the copper-exposed organisms. Increased apoptosis is supported by the increase in lysosomal membrane destabilisation in the copper-exposed snails. Transcriptomic changes relating to apoptosis, phagocytosis, protein degradation and the lysosome were evident and these processes can be linked to the degradation of post-apoptotic debris. The study identified contaminant specific transcriptomic markers as well as markers of general stress. From an ecotoxicological perspective, the use of a framework to group transcriptomic responses into those associated with copper transport, survival and cell death assisted with the complex process of interpretation of RNA-seq data. The broad adoption of such a framework in ecotoxicology studies would assist in comparison between studies and the identification of reliable transcriptomic markers of contaminant exposure and response. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression patterns in the progression of canine copper-associated chronic hepatitis

PubMed Central

Dirksen, Karen; Spee, Bart; Penning, Louis C.; van den Ingh, Ted S. G. A. M.; Burgener, Iwan A.; Watson, Adrian L.; Groot Koerkamp, Marian; Rothuizen, Jan

2017-01-01

Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver’s first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible. PMID:28459846

Lead, cadmium, chromium, cobalt, and copper in chicken feathers from Tuskegee, Alabama

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, A.T.; Love, M.J.; Booker, T.

1994-12-31

The feather has been widely used as a indicator tissue of metal exposure in birds. The feathers were collected from Tuskegee University poultry farm (TUPF) and Harrison Poultry farm (HPF) chicken and analyzed by Inductively Coupled Plasma Atomic Emission Spectroscopy for lead, cadmium, cobalt, chromium, and copper contaminations. The mean levels of lead, cadmium, cobalt, chromium, and copper in TUPF chicken were 3.67, 0.13, 12.23, 0.22, and 7.71 ppm, respectively, and in HPF chicken were 5.32, 0.096, 11.03, 0.15, and 8.06 ppm, respectively. The mean levels of these metals did not show any significant difference between TUPF and HPF chicken.

Zinc and copper bioaccumulation in fish from Laizhou Bay, the Bohai Sea

NASA Astrophysics Data System (ADS)

Liu, Jinhu; Cao, Liang; Huang, Wei; Zhang, Chuantao; Dou, Shuozeng

2014-05-01

Zinc (Zn) and copper (Cu) concentrations were determined in the tissues (muscle, stomach, liver, gills, skin, and gonads) of five commercial fish species (mullet Liza haematocheilus, flathead Platycephalus indicus, mackerel Scomberomorus niphonius, silver pomfret Pampus argenteus, and sea bass Lateolabrax japonicus) from Laizhou Bay in the Bohai Sea. Metal bioaccumulation was highest in the metabolically active tissues of the gonads and liver. Bioconcentration factors for Zn were higher in all tissues (gonads 44.35, stomach 7.73, gills 7.72, liver 5.61, skin 4.88, and muscle 1.63) than the corresponding values for Cu (gonads 3.50, stomach 3.00, gills 1.60, liver 5.43, skin 1.50, and muscle 0.93). Mackerel tissues accumulated metal to higher concentrations than did other fish species, but bioaccumulation levels were not significantly correlated with the trophic levels of the fish. Zn and Cu concentrations in the tissues were generally negatively correlated with fish length, except for a few tissues of sea bass. Risk assessment based on national and international permissible limits and provisional tolerances for weekly intake of Zn and Cu revealed that the concentrations of these two metals in muscle were relatively low and would not pose hazards to human health.

Carbohydrate metabolism in erythrocytes of copper deficient rats.

PubMed

Brooks, S P J; Cockell, K A; Dawson, B A; Ratnayake, W M N; Lampi, B J; Belonje, B; Black, D B; Plouffe, L J

2003-11-01

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans.

PubMed

Chun, Haarin; Sharma, Anuj Kumar; Lee, Jaekwon; Chan, Jefferson; Jia, Shang; Kim, Byung-Eun

2017-01-06

Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantitative mapping of elemental distribution in leaves of the metallophytes Helichrysum candolleanum, Blepharis aspera, and Blepharis diversispina from Selkirk Cu-Ni mine, Botswana

NASA Astrophysics Data System (ADS)

Koosaletse-Mswela, Pulane; Przybyłowicz, Wojciech J.; Cloete, Karen J.; Barnabas, Alban D.; Torto, Nelson; Mesjasz-Przybyłowicz, Jolanta

2015-11-01

Multi-element profiling is essential in understanding the metal-tolerant behavior of metallophytes. Although previous reports using multi-elemental analyses show that the metallophytes Blepharis aspera, Blepharis diversispina (Acanthaceae) and Helichrysum candolleanum (Asteraceae) take up metals, no information exists on elemental spatial distribution and concentrations in specific tissues of these plants. The aim of this study therefore was to assess the spatial distribution and concentration of copper, nickel and other elements in leaf tissues of these plants using micro-PIXE. Whole plants were collected with soil in pots from an operational copper and nickel mine (i.e., a copper and nickel mineralized area), Selkirk, about 40 km north-east of Francistown, Botswana. On the same day the samples were transported by air to iThemba LABS in South Africa. Leaf specimens were cryofixed in liquid propane cooled by LN2. Parallel samples were embedded in resin for anatomical studies to facilitate interpretation of elemental maps. The distribution and concentration of copper, nickel, and other elements in leaf tissues were determined using micro-PIXE and proton backscattering spectrometry. Data evaluation was performed using GeoPIXE II software. Micro-PIXE showed that H. candolleanum had the highest whole leaf content of copper (70 ± 3 μg g-1 DW) and nickel (168 ± 5 μg g-1 DW), followed by B. aspera (Cu: 25 ± 1 μg g-1 DW; Ni: 166 ± 4 μg g-1 DW) and B. diversispina (Cu: 3 ± 1 μg g-1 DW; Ni, below detection limit). For specific leaf tissues, the highest levels of copper were found in the vascular bundle for H. candolleanum (167 ± 7 μg g-1 DW) and the lower epidermis for B. aspera (70 ± 9 μg g-1 DW). The highest levels of nickel were present in the vascular bundle of B. aspera (479 ± 10 μg g-1 DW) and H. candolleanum (90 ± 5 μg g-1 DW). Elemental maps showed a similar distribution pattern for copper and nickel in B. aspera and B diversispina, with these elements concentrated in the upper and lower epidermal regions. However, for H. candolleanum, both copper and nickel were concentrated in the mesophyll. The difference in concentration and accumulation patterns between B. aspera, B. diversispina and H. candolleanum suggests that the metal-tolerant adaptation of these metallophytes may differ.

Accumulation and effects of copper on aquatic macrophytes Potamogeton pectinatus L.: Potential application to environmental monitoring and phytoremediation.

PubMed

Costa, Marcela Brandão; Tavares, Francesca Valêncio; Martinez, Claudia Bueno; Colares, Ioni Gonçalves; Martins, Camila de Martinez Gaspar

2018-07-15

This study investigated the ability of Potamogeton pectinatus L. to accumulate copper and its effects on plants. In accumulation tests, macrophytes were exposed (96 h) to different copper concentrations (0-1000 µM) and the metal was measured in media and plant tissues (roots, stems and leaves) to determine the bioconcentration factor (BCF). Plants accumulated high concentrations of copper in a dose-dependent manner and roots was the main organ for copper accumulation. However, the more copper increased in water, the more BCF values decreased. It may be due to either saturation of copper uptake or down-regulation of metal uptake by plants. In the physiological and morphological analyses, plants were kept (96 h) in Hoagland nutrient solution without copper, in full Hoagland solution (0.5 µM Cu) and in Hoagland medium with copper from 1 to 100 µM. The absence and the presence of copper above to 1 µM inhibited photosynthesis. Chlorophylls and carotenoid levels also decreased with the excess of copper, a fact that may have affected the photosystem II-dependent of chlorophyll and caused photosynthesis suppression. Only macrophytes at 10 µM Cu showed decrease in length and number of leaves on the 10th day of the test, when they died. Chlorosis and necrosis were observed in control groups and groups with extra copper, but not in Hoalgand group. Overall, the macrophyte P. pectinatus can be considered a suitable plant for monitoring environments contaminated by copper, based on results of copper accumulation in the plant, decrease in pigment concentration and presence of chlorosis and necrosis. However, values of BCF based on fresh water tissues was not proper to indicate the use of P. pectinatus for cleaning environments contaminated by copper. Copyright © 2018 Elsevier Inc. All rights reserved.

Undergraduates in the lab: Analyzing metal and organic contaminants in oysters and sediments from southeastern North Carolina

NASA Astrophysics Data System (ADS)

Mead, R. N.; Kipp, L. E.; Liberatore, H.; Sherard, S.; Steagall, M.; Skrabal, S. A.

2016-02-01

A state-funded project to analyze a suite of metal and organic contaminants in oyster tissues and ambient sediments was carried out nearly exclusively by over 10 undergraduates at the University of North Carolina Wilmington. This study will present Concentrations of various trace metals (most notably arsenic, copper, mercury, and zinc) and organic contaminants (polycyclic aromatic hydrocarbons and the antibacterial, triclosan) have been determined in oyster tissues and adjacent sediments in New Hanover and Brunswick counties, southeastern North Carolina. Trace metals that exceeded national median levels at multiple sites in this study included arsenic, copper, and zinc. Elevated levels of arsenic (exceeding the national median and, often, the national 85th percentiles) in oyster tissues are characteristic of much of the southeastern United States; these elevations are attributed to high natural background levels in the underlying bedrock and sediments as well as historical contamination by arsenic-containing agricultural pesticides. Another metal of national concern is mercury; however, concentrations of this metal were mostly at the national median for oyster tissue. Polycyclic aromatic hydrocarbons (PAHs) barely exceeded or were near the national median at only 3 sites, 2 in Lockwood Folly estuary, Brunswick County and 1 at Bradley Creek, New Hanover County. Concentrations at the remaining sites were 4 to >10 times less than the national median. Triclosan, an antibacterial compound used in many consumer products, was found in oyster tissues and sediments at the 4 sites at which it was examined. Oyster tissues contained triclosan at levels 2 to 43 times as high as adjacent sediments, indicating its bioaccumulation potential. Levels of metals and PAHs in oyster tissues are consistently elevated near more urbanized areas but are unlikely to be at levels harmful for human consumption.

Overexpression of amyloid precursor protein increases copper content in HEK293 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suazo, Miriam; Hodar, Christian; Morgan, Carlos

2009-05-15

Amyloid precursor protein (APP) is a transmembrane glycoprotein widely expressed in mammalian tissues and plays a central role in Alzheimer's disease. However, its physiological function remains elusive. Cu{sup 2+} binding and reduction activities have been described in the extracellular APP135-156 region, which might be relevant for cellular copper uptake and homeostasis. Here, we assessed Cu{sup 2+} reduction and {sup 64}Cu uptake in two human HEK293 cell lines overexpressing APP. Our results indicate that Cu{sup 2+} reduction increased and cells accumulated larger levels of copper, maintaining cell viability at supra-physiological levels of Cu{sup 2+} ions. Moreover, wild-type cells exposed to bothmore » Cu{sup 2+} ions and APP135-155 synthetic peptides increased copper reduction and uptake. Complementation of function studies in human APP751 transformed Fre1 defective Saccharomyces cerevisiae cells rescued low Cu{sup 2+} reductase activity and increased {sup 64}Cu uptake. We conclude that Cu{sup 2+} reduction activity of APP facilitates copper uptake and may represent an early step in cellular copper homeostasis.« less

Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

PubMed

Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

2017-01-01

Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

Does Dietary Copper Supplementation enhance or diminish PCB126 Toxicity in Rodent Liver?

PubMed Central

Lai, Ian K.; Klaren, William D.; Li, Miao; Wels, Brian; Simmons, Donald L.; Olivier, Alicia K.; Haschek, Wanda M.; Wang, Kai; Ludewig, Gabriele; Robertson, Larry W.

2013-01-01

Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 μmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats the hallmark signs of AhR activation were present, including increased cytochrome P-450 and lipid levels, and decreased glutathione. In addition a doubling of hepatic copper levels was seen and overall metals homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD) or increased (tyrosinase, metallothionein 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e. oxidative stress and steatosis, is clearly associated with disturbed metals homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists. PMID:23527585

In utero copper treatment for Menkes disease associated with a severe ATP7A mutation

PubMed Central

Haddad, Marie Reine; Macri, Charles J.; Holmes, Courtney S.; Goldstein, David S.; Jacobson, Beryl E.; Centeno, Jose A.; Popek, Edwina J.; Gahl, Willam A.; Kaler, Stephen G.

2012-01-01

Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect. In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5 weeks gestational age. Copper histidine (900 μg per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17 μg/dL prior to treatment to 45 μg/dL, and ceruloplasmin levels from 39 mg/L to 122 mg/L. After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5 weeks and daily copper histidine therapy (250 μg sc b.i.d.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5 months of age. The patient’s ATP7A mutation, which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Western blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances. PMID:22695177

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gough, Mallory, E-mail: m.gough1@lancaster.ac.uk; Blanthorn-Hazell, Sophee, E-mail: s.blanthorn-hazell@lancaster.ac.uk; Delury, Craig, E-mail: c.delury@lancaster.ac.uk

Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enablemore » cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.« less

Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration

PubMed Central

Crowe, Andrew; Jackaman, Connie; Beddoes, Katie M.; Ricciardo, Belinda; Nelson, Delia J.

2013-01-01

Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an anti-angiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes. PMID:24013775

Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Vijay; Kalita, Jayantee, E-mail: jayanteek@yahoo.com; Bora, Himangsu K.

Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO{sub 4}) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range = 205 ± 10 g) were equally divided into three groups. CuSO{sub 4} was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200 mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the endmore » of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO{sub 4} resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO{sub 4} exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration. - Highlights: • Oral dosing of CuSO{sub 4} leads to oxidative stress in liver, brain and kidney. • Liver has maximum oxidative stress followed by brain and kidney. • Oxidative stress correlated with the respective organ dysfunction and tissue Cu concentration.« less

The efficacy of deferiprone on tissues aluminum removal and copper, zinc, manganese level in rabbits.

PubMed

Liu, Ping; Yao, Yu-Na; Wu, Shi-De; Dong, Huai-Jun; Feng, Guo-Chang; Yuan, Xiao-Yan

2005-08-01

The effect of 1,2-dimethyl-3-hydroxypyrid-4-one [deferiprone (DE)] on aluminum mobilization and elimination from tissues and serum as well as the influence on the excretion of trace elements, copper, zinc and manganese in rabbits was investigated. Sixteen New Zealand rabbits were randomly divided into three groups: control, Al-only and Al+DE. The Al-only and Al+DE animals received injections of Al2(SO43.18H2O 600 micromol Al/kg 5 days per week for 3 weeks. One week after the last Al injection the Al+DE rabbits were given deferiprone 750 micromol/kg/day intragastrically for 2 weeks. At the 42nd day the animals were sacrificed and the organs were taken and digested. Blood was taken from the ear artery three times (at the initiation of the experiment, before and after deferiprone administration). The aluminum and copper, zinc, manganese were determined by atomic absorption spectrophotometry. Our results showed that deferiprone could highly mobilize aluminum stores from tissues. At the end of experiment the aluminum contents of bone, kidney, liver and brain in Al+DE were significantly lower than that in Al-only rabbits. The copper, zinc, manganese contents were not affected by deferiprone administration.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

PubMed

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

Protective Effects of Lactobacillus plantarum CCFM8246 against Copper Toxicity in Mice

PubMed Central

Li, Xiaoxiao; Zhai, Qixiao; Wang, Gang; Zhang, Qiuxiang; Zhang, Hao; Chen, Wei

2015-01-01

Lactobacillus plantarum CCFM8246, which has a relatively strong copper binding capacity and tolerance to copper ions, was obtained by screening from 16 lactic acid bacteria in vitro. The selected strain was then applied to a mouse model to evaluate its protective function against copper intoxication in vivo. The experimental mice were divided into an intervention group and a therapy group; mice in the intervention group received co-administration of CCFM8246 and a copper ion solution by gavage, while mice in the therapy group were treated with CCFM8246 after 4 weeks of copper exposure. In both two groups, mice treated with copper alone and that treated with neither CCFM8246 nor copper served as positive and negative controls, respectively. At the end of the experimental period, the copper content in feces and tissues, the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and oxidation stress indices in liver and kidney tissue were determined. Learning and memory ability was evaluated by Morris water maze experiments. The results indicated that treatment with CCFM8246 significantly increased the copper content in feces to promote copper excretion, reduce the accumulation of copper in tissues, reverse oxidative stress induced by copper exposure, recover the ALT and AST in serum and improve the spatial memory of mice. PMID:26605944

Copper Acquisition and Utilization in Fungi.

PubMed

Smith, Aaron D; Logeman, Brandon L; Thiele, Dennis J

2017-09-08

Fungal cells colonize and proliferate in distinct niches, from soil and plants to diverse tissues in human hosts. Consequently, fungi are challenged with the goal of obtaining nutrients while simultaneously elaborating robust regulatory mechanisms to cope with a range of availability of nutrients, from scarcity to excess. Copper is essential for life but also potentially toxic. In this review we describe the sophisticated homeostatic mechanisms by which fungi acquire, utilize, and control this biochemically versatile trace element. Fungal pathogens, which can occupy distinct host tissues that have their own intrinsic requirements for copper homeostasis, have evolved mechanisms to acquire copper to successfully colonize the host, disseminate to other tissues, and combat host copper bombardment mechanisms that would otherwise mitigate virulence.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leite, Carlos Eduardo, E-mail: carlos.leite@pucrs.br; Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, CEP 90035-003; Maboni, Lucas de Oliveira

The use of zebrafish (Danio rerio) is increasing as an intermediate preclinical model, to prioritize drug candidates for mammalian testing. As the immune system of the zebrafish is quite similar to that of mammals, models of inflammation are being developed for the screening of new drugs. The characterization of these models is crucial for studies that seek for mechanisms of action and specific pharmacological targets. It is well known that copper is a metal that induces damage and cell migration to hair cells of lateral line of zebrafish. Extracellular nucleotides/nucleosides, as ATP and adenosine (ADO), act as endogenous signaling moleculesmore » during tissue damage by exerting effects on inflammatory and immune responses. The present study aimed to characterize the inflammatory status, and to investigate the involvement of the purinergic system in copper-induced inflammation in zebrafish larvae. Fishes of 7 days post-fertilization were exposed to 10 μM of copper for a period of 24 h. The grade of oxidative stress, inflammatory status, copper uptake, the activity and the gene expression of the enzymes responsible for controlling the levels of nucleotides and adenosine were evaluated. Due to the copper accumulation in zebrafish larvae tissues, the damage and oxidative stress were exacerbated over time, resulting in an inflammatory process involving IL-1β, TNF-α, COX-2 and PGE{sub 2}. Within the purinergic system, the mechanisms that control the ADO levels were the most involved, mainly the reactions performed by the isoenzyme ADA 2. In conclusion, our data shed new lights on the mechanisms related to copper-induced inflammation in zebrafish larvae. - Graphical abstract: This scheme provides a chronological proposition for the biochemical events induced by copper in zebrafish larvae. The dashed line shows the absorption of copper over the exposure time. After 1 h of exposure to copper, the release of PGE{sub 2} occurs, followed by an increase of MPO (as a consequence of neutrophil migration), increased expression of genes involved in inflammatory events (IL-1β and TNF-α) and, reduction of the anti-inflammatory cytokine IL-10 at 4 h. At 24 h, the copper concentration is found highly increased, what is coincident with oxidative stress. Regarding the purinergic system, it is possible to observe an inhibition of ecto-5′-NT and ADA, with the consequent increase of AMP and ADA, respectively, at 24 h. The expression of enzyme-related genes shows a decrease in the expression of ecto-5′-NT and variable expressions of ADA subfamily enzymes. - Highlights: • Copper led to increased oxidative stress, and decreased the antioxidants' defenses. • Copper induced time-related changes of IL-1β, TNF-α, IL-10 and PGE{sub 2} levels. • ADA activity controls the levels of adenosine in copper-induced inflammation. • ADA 2 is the main ADA subfamily involved. • The purinergic system seems to be involved in the resolution of inflammation.« less

Angiogenesis in calcium phosphate scaffolds by inorganic copper ion release.

PubMed

Barralet, Jake; Gbureck, Uwe; Habibovic, Pamela; Vorndran, Elke; Gerard, Catherine; Doillon, Charles J

2009-07-01

Angiogenesis in a tissue-engineered device may be induced by incorporating growth factors (e.g., vascular endothelial growth factor [VEGF]), genetically modified cells, and=or vascular cells. It represents an important process during the formation and repair of tissue and is essential for nourishment and supply of reparative and immunological cells. Inorganic angiogenic factors, such as copper ions, are therefore of interest in the fields of regenerative medicine and tissue engineering due to their low cost, higher stability, and potentially greater safety compared with recombinant proteins or genetic engineering approaches. The purpose of this study was to compare tissue responses to 3D printed macroporous bioceramic scaffolds implanted in mice that had been loaded with either VEGF or copper sulfate. These factors were spatially localized at the end of a single macropore some 7 mm from the surface of the scaffold. Controls without angiogenic factors exhibited only poor tissue growth within the blocks; in contrast, low doses of copper sulfate led to the formation of microvessels oriented along the macropore axis. Further, wound tissue ingrowth was particularly sensitive to the quantity of copper sulfate and was enhanced at specific concentrations or in combination with VEGF. The potential to accelerate and guide angiogenesis and wound healing by copper ion release without the expense of inductive protein(s) is highly attractive in the area of tissue-engineered bone and offers significant future potential in the field of regenerative biomaterials.

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

PubMed Central

2014-01-01

Background Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. Methods Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. Results Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of intracellular (IC) copper delivery via the copper chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which normalized SOD1 activity with consequent bolstering of anti-oxidant defenses. Furthermore, diabetes depressed levels of additional intracellular copper-transporting proteins, including antioxidant-protein-1 (ATOX1) and copper-transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1 (ATP7A). Conclusions Myocardial copper deficiency and defective cellular copper transport/trafficking are revealed as key molecular defects underlying LV impairment in diabetes, and TETA-mediated restoration of copper regulation provides a potential new class of therapeutic molecules for DCM. PMID:24927960

Factors that Affect the Content of Cadmium, Nickel, Copper and Zinc in Tissues of the Knee Joint.

PubMed

Roczniak, Wojciech; Brodziak-Dopierała, Barbara; Cipora, Elżbieta; Jakóbik-Kolon, Agata; Kluczka, Joanna; Babuśka-Roczniak, Magdalena

2017-08-01

Osteoarthritis causes the degradation of the articular cartilage and periarticular bones. Trace elements influence the growth, development and condition of the bone tissue. Changes to the mineral composition of the bone tissue can cause degenerative changes and fractures. The aim of the research was to determine the content of cadmium (Cd), nickel (Ni), copper (Cu) and zinc (Zn) in the tibia, the femur and the meniscus in men and women who underwent a knee replacement surgery. Samples were collected from 50 patients, including 36 women and 14 men. The determination of trace elements content were performed by ICP-AES method, using Varian 710-ES. Average concentration in the tissues of the knee joint teeth amounted for cadmium 0.015, nickel 0.60, copper 0.89 and zinc 80.81 mg/kg wet weight. There were statistically significant differences in the content of cadmium, copper and zinc in different parts of the knee joint. There were no statistically significant differences in the content of cadmium, nickel, copper and zinc in women and men in the examined parts of the knee joint. Among the elements tested, copper and nickel showed a high content in the connective tissue (the meniscus) compared to the bone tissue (the tibia and the femur).

Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses in vivo

PubMed Central

Wei, Hao; Beckman, Joseph S.; Zhang, Wei-Jian

2011-01-01

Redox-active transition metal ions, such as iron and copper, may play an important role in vascular inflammation, which is an etiologic factor in atherosclerotic vascular diseases. In this study, we investigated whether tetrathiomolybdate (TTM), a highly specific copper chelator, can act as an anti-inflammatory agent, preventing lipopolysaccharide (LPS)-induced inflammatory responses in vivo. Female C57BL/6N mice were daily gavaged with TTM (30 mg/kg body wt) or vehicle control. After 3 wk, animals were injected intraperitoneally with 50 μg LPS or saline buffer and killed 3 h later. Treatment with TTM reduced serum ceruloplasmin activity by 43%, a surrogate marker of bioavailable copper, in the absence of detectable hepatotoxicity. The concentrations of both copper and molybdenum increased in various tissues, whereas the copper-to-molybdenum ratio decreased, consistent with reduced copper bioavailability. TTM treatment did not have a significant effect on superoxide dismutase activity in heart and liver. Furthermore, TTM significantly inhibited LPS-induced inflammatory gene transcription in aorta and heart, including vascular and intercellular adhesion molecule-1 (VCAM-1 and ICAM-1, respectively), monocyte chemotactic protein-1 (MCP-1), interleukin-6, and tumor necrosis factor (TNF)-α (ANOVA, P < 0.05); consistently, protein levels of VCAM-1, ICAM-1, and MCP-1 in heart were also significantly lower in TTM-treated animals. Similar inhibitory effects of TTM were observed on activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) in heart and lungs. Finally, TTM significantly inhibited LPS-induced increases of serum levels of soluble ICAM-1, MCP-1, and TNF-α (ANOVA, P < 0.05). These data indicate that copper chelation with TTM inhibits LPS-induced inflammatory responses in aorta and other tissues of mice, most likely by inhibiting activation of the redox-sensitive transcription factors, NF-κB and AP-1. Therefore, copper appears to play an important role in vascular inflammation, and TTM may have value as an anti-inflammatory or anti-atherogenic agent. PMID:21724870

Evaluating toxicity of copper(II) oxide nanoparticles (CuO-NPs) through waterborne exposure to tilapia (Oreochromis mossambicus) by tissue accumulation, oxidative stress, histopathology, and genotoxicity.

PubMed

Shahzad, Khurram; Khan, Muhammad Naeem; Jabeen, Farhat; Kosour, Nasreen; Chaudhry, Abdul Shakoor; Sohail, Muhammad

2018-06-01

Metal oxide nanoparticles are widely used in industries, and peak level can be confirmed in their surroundings. In the present study, the sub-lethal effects of CuO-NPs from low to high concentration as 0.5 to 1.5 mg/L were observed in tilapia (Oreochromis mossambicus). Accumulation of copper from CuO-NPs was increased with the increase in doses, and maximum accumulation was found in the gill than liver and muscles. The increased lipid peroxidation level was observed in the gill as compared to liver, and the similar results were obtained in catalase and glutathione while superoxide dismutase level was higher in the liver than gills. In histological alterations, gill edema, curved tips, fusion of gill lamellae, and thickening of primary and secondary gill lamellae were observed. Necrosis and apoptosis with condensed nuclear bodies and pyknotic nuclei were observed in the liver at the highest dose concentration. In a genotoxic study, the highest value of % tail DNA and olive tail movement was observed with increasing concentrations. Copper oxide nanoparticles has greater potential to accumulate in the soft tissues, which may cause respiratory distress such as oxidative stress, induction of antioxidant defense by raising glutathione, organ pathology, and genotoxicity.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma

PubMed Central

Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-01-01

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies. PMID:29507693

Heavy metal contaminants in tissues of the garfish, Belone belone L., 1761, and the bluefish, Pomatomus saltatrix L., 1766, from Turkey waters.

PubMed

Türkmen, Aysun; Tepe, Yalçin; Türkmen, Mustafa; Mutlu, Ekrem

2009-01-01

Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. Fish samples were collected through the coastal waters of Turkey and the contents of cadmium, cobalt, chrome, copper, iron, manganese, nickel, zinc and lead in the liver and muscle tissues were determined. Among the metals analyzed, copper, zinc and iron were the most abundant in the different tissues while cadmium and lead were the least abundant both in Belone belone and Pomatomus saltatrix. Metal concentrations in muscles of fish species were found 0.01-0.38 mg kg(-1) for cadmium, 0.01-0.53 mg kg(-1) for cobalt, 0.05-1.87 mg kg(-1) for chromium, 0.21-5.89 mg kg(-1) for copper, 9.99-43.3 mg kg(-1) for iron, 0.14-1.33 mg kg(-1) for manganese, 0.06-4.70 mg kg(-1) for nickel, 0.09-0.81 mg kg(-1) for lead, 3.85-15.9 mg kg(-1) for zinc, respectively. Regional changes in metal concentration were observed in the tissues of both species, but these variations may not influence consumption advisories.

Accumulation of heavy metals and As in liver, hair, femur, and lung of Persian jird (Meriones persicus) in Darreh Zereshk copper mine, Iran.

PubMed

Khazaee, Manoochehr; Hamidian, Amir Hossein; Alizadeh Shabani, Afshin; Ashrafi, Sohrab; Mirjalili, Seyyed Ali Ashghar; Esmaeilzadeh, Esmat

2016-02-01

Rodents frequently serve as bioindicator to monitor the quality of the environment. Concentrations of 11 elements (Cd, Co, Ti, Fe, Mn, Cu, Sb, As, Sr, Ni, and Cr) were investigated and compared in liver, hair, femur, and lung of the Persian jird (Meriones persicus) from Darreh Zereshk copper mine, Iran. Metals were determined in different tissues of 39 individuals of Persian jird, collected by snap trap in 2014 from five areas of Darreh Zereshk copper mine. Samples were prepared by wet digestion method, and the contents of elements were analyzed with ICP-OES (VARIAN, 725-ES) instrument. Cadmium, Sb, and Co were below the limit of detection, and Mn and As were found only in hair and liver tissues. We detected the highest concentration of Cu, As, Ti, Fe, Mn, Cr, and Ni in hair in comparison with other tissues. Significant higher levels of Ti in femur and hair; Fe in liver and hair; Mn in liver; As in hair; Sr in lung; Cr in lung, hair, femur, and liver; Cu in femur; and Ni in liver and lung tissues were observed in females. Nearly all element concentrations in the tissues of Persian jird from flotation site, Darreh Zereshk and Hasan Abad villages and leaching site (mining areas) were higher than those from tailing dump site (reference site). We found the highest concentrations of As in liver and hair; Ni and Cr in liver, hair, and lung; and Sr in lung and hair tissues of Persian jird in leaching site. We tried to specify the status of elements before fully exploitation of Darreh Zereshk copper mine by using bioindicator species. Based on our achievements, initial activities did not strongly pollute the surrounded environment of the mine. The high abundance of Persian jird as well as their several proper features makes them a suitable species for biomonitoring programs especially for further studies will be performed after full exploitation of Darreh Zereshk copper mine.

Heavy metal concentrations in Squilla mantis (L.) (Crustacea, Stomatopoda) from the gulf of cadiz evaluation of the impact of the Aznalcollar mining spill.

PubMed

Blasco, J; Arias, A M; Sáenz, V

2002-04-01

After the Aznalcóllar mining spill (25th April 1998), considerable social concern arose amongst the inhabitants of the SW Iberian Peninsula concerning the consumption of local seafood. Squilla mantis was collected in four regions of the Gulf of Cádiz with a dual objective: to analyze the heavy metal levels for human consumption and as part of biomonitoring program. Heavy metal concentrations (Fe, Mn, Zn, Cu, Cd and Pb) were analyzed in soft tissues and cuticle. The highest values were found in the soft tissues for zinc, copper and cadmium and in the cuticle for iron, manganese and lead. The mean copper concentration in the soft tissue, corresponding to the edible part, was 27.1 microg x g(-1) wet weight. Approximately 80% of stations showed values higher than 20 microg x g(-1) wet weight of copper, the Spanish legal limit for the concentration of this metal in the crustacean for human consumption. For Zn and Cu no significant differences were found between regions, probably related with the capacity for regulation of S. mantis. The highest values found for copper in the Gulf of Cádiz compared to other areas is likely to be related with contamination from terrestrial mining activities (copper and pyrites) in the region, dating back to the times of Tartessians and Romans, rather than the effects of mining spill which was shown not to create any significant increases in heavy metal concentrations of organisms of the Guadalquivir River or the adjacent coastal area.

Interactions between accumulated copper, bacterial community structure and histamine levels in crayfish meat during storage.

PubMed

Soedarini, Bernadeta; van Gestel, Cornelis A M; van Straalen, Nico M; Widianarko, Budi; Röling, Wilfred F M

2014-08-01

Pollution in aquaculture areas may negatively impact edible species and threaten seafood quality and safety. The aim of this study was to determine the interaction between copper and bacteria in the aquatic habitat and their impact upon crustaceans. Marbled crayfish was chosen as a model of aquatic crustaceans and the influence of metal contamination on bacterial community structure in water used to culture crayfish and in crayfish themselves was investigated. Histamine, an allergen commonly formed by certain groups of bacteria in crustacean edible tissue during storage, was also determined. Copper exposure increased its concentration in crayfish meat by 17.4%, but the copper concentration remained within acceptable food safety limits. Elevated copper levels affected the bacterial community both in the water used to cultivate crayfish and in the marbled crayfish themselves. Cluster analysis of 16S rRNA-gene based microbial community fingerprints revealed that copper impacted the bacterial community in the water and in the crayfish meat. However, copper exposure reduced the formation of histamine in crayfish meat during storage by 66.3%. Copper from the habitat appears to reduce histamine accumulation in crayfish meat during storage by affecting the bacterial community structure of the cultivation water and most likely also in the intestine of the crayfish. From a food safety point of view, copper treatment during the aqua culturing of crustaceans has a positive impact on the postharvest stage. © 2013 Society of Chemical Industry.

Cadmium, copper, lead and zinc in cultured oysters under two contrasting climatic conditions in coastal lagoons from SE Gulf of California, Mexico.

PubMed

Osuna-Martínez, Carmen C; Páez-Osuna, Federico; Alonso-Rodríguez, Rosalba

2011-09-01

In order to determine the metal concentrations in cultured oysters from four coastal lagoons from SE Gulf of California, several individuals of Crassostrea gigas and C. corteziensis were collected and their cadmium, copper, lead and zinc levels were measured by atomic absorption spectrometry after acid digestion. The concentration of metals in oyster soft tissue was Zn > Cu > Cd > Pb. In two lagoons, Cd concentrations (10.1-13.5 μg g(-1) dw) exceeded the maximum level allowed according to the Official Mexican Standard (NOM-031-SSA1-1993), which is equivalent to the WHO recommended Cd levels in organisms used for human consumption.

Studies on the feeding of cupric sulfate pentahydrate and cupric citrate to broiler chickens.

PubMed

Pesti, G M; Bakalli, R I

1996-09-01

Male commercial broiler strain chickens were fed either a control diet (based on corn and soybean meal) or the control diet supplemented with cupric sulfate pentahydrate or cupric citrate in seven experiments (six in floor pens, one in wire-floored batteries). In Experiment 1, feeding 125 or 250 mg/kg copper increased growth (4.9%) and decreased feed conversion ratios (3.4%), total plasma cholesterol (40.2%), and breast muscle cholesterol (37.0%). Feeding 375 mg/kg copper was without further beneficial effect. In Experiment 2, withdrawing growth promoting supplements of copper from the feed for the last 7 d caused a significant (P < 0.05) increase in breast muscle cholesterol at 42 d of age: 57.2, 48.0, and 43.2 mg/100 g meat for birds supplemented for 0, 35, or 42 d, respectively. Feeding 10 vs 260 mg/kg copper caused only small increases in tissue copper levels: 0.36 vs 0.41 mg/kg for breast meat, and 0.48 vs 0.60 mg/kg for thigh meat, respectively. Litter copper accumulations in these experiments were similar to those of earlier reports. Breast muscle cholesterol was reduced by feeding 125 mg/kg supplemental copper from cupric citrate (27.84 mg/100 g) or 125 mg supplemental copper from cupric sulfate pentahydrate (25.32 mg/100 g) compared to broilers fed the control diet (43.92 mg/100 g). Cupric citrate was efficacious for growth promotion at lower copper levels than cupric sulfate pentahydrate, resulting in reduced litter copper.

Comparative evaluation of micronutrient status in the serum of diabetes mellitus patients and healthy individuals with periodontitis

PubMed Central

Thomas, Biju; Kumari, Suchetha; Ramitha, K.; Ashwini Kumari, M. B.

2010-01-01

Background: Periodontal diseases are microbial induced chronic inflammatory conditions characterized by infiltration of leukocytes, loss of connective tissue, alveolar bone resorption, and formation of periodontal pockets. In response to periodontal pathogens, the leukocytes (PMN) elaborate destructive oxidants, proteinases and other factors. The balance between these factors, the antioxidants and endogenously synthesized antiproteinases determine the extent of periodontal damage. Diabetes mellitus is a metabolic disorder. Most of the complications of diabetes are due to hyperglycemia. Persons with diabetes are at a greater risk for periodontal disease Malnutrition is characterized by marked tissue depletion of antioxidant nutrients and impaired acute phase protein response to infections resulting in impaired healing. Diabetes mellitus also alters the micronutrient levels. Malnutrition is characterized by marked tissue depletion of antioxidant nutrients and impaired acute phase protein response to infections resulting in impaired healing. Malnutrition, which usually involves concomitant deficiencies of several essential macro and micro nutrients, therefore, has the potential to adversely influence the prognosis of periodontal infections. Objectives:This study has been conducted to evaluate and compare the serum levels of vitamin C, zinc and copper in diabetic and healthy individuals with periodontitis. Materials and Methods: In this case control study 60 subjects inclusive of both sexes were selected and divided into 3 groups of 20 each. Group 1 comprised of 20 subjects with type 2 diabetes mellitus and periodontal disease, Group 2 comprised of 20 healthy subjects with periodontal disease. And Group 3 comprised of 20 healthy subjects without periodontal disease. Venous blood samples were collected and centrifuged at 3000rpm for 15 minutes and the superanatant serum is collected to measure the vitamin C, zinc and copper levels. The vitamin C levels of clinical samples were measured using spectrophotometric quantitation (dinitrophenyl hydrazine method) and zinc and copper levels were measured using atomic absorption spectrophotometry. Results: The results showed that the levels of vitamin C and zinc decreased and copper levels increased in diabetic patients with periodontits compared to healthy individuals with periodontitis. Conclusion: It may be reasonable to suggest vitamin and/or mineral supplements for patients whose nutrition might be inadequate. Future research should focus on an evaluation of which nutrients may help to prevent the onset and progression of periodontal disease PMID:20922079

Pixe analysis of trace elements in tissues of rats treated with anticonvulsants

NASA Astrophysics Data System (ADS)

Hurd, R. W.; Van Rinsvelt, H. A.; Kinyua, A. M.; O'Neill, M. P.; Wilder, B. J.; Houdayer, A.; Hinrichsen, P. F.

1987-04-01

Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

Tear copper and its association with liver copper concentrations in six adult ewes.

PubMed Central

Schoster, J V; Stuhr, C; Kiorpes, A

1995-01-01

Tear and liver copper concentrations from 6 clinically healthy adult mixed-breed ewes were measured by Atomic Absorption Electrothermal Atomization (graphite furnace) Spectrometry and Flame Absorption Spectrometry, respectively, 7 times over 227 d to determine if their tears contained copper and if so, whether tear copper concentrations could reliably predict liver copper concentrations. To produce changes in liver copper concentration, the diet was supplemented with copper at concentrations that increased from 23 mg to 45 mg Cu/kg feed/day/sheep during the study. This regimen raised liver copper for all sheep to potentially toxic hepatic tissue concentration of greater than 500 mg/kg dry (DM) matter (tissue). The results of the study showed that copper was present in the tears of all sheep. The mean tear copper concentration showed a positive correlation with liver copper concentration (P = 0.003), increasing from 0.07 mg/kg DM at the start to 0.44 mg/kg DM at the end of the study, but could not reliably predict liver copper concentration (R2 = 0.222). PMID:7648525

Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

PubMed

Cavallieri, Francesco; Fini, Nicola; Contardi, Sara; Fiorini, Massimo; Corradini, Elena; Valzania, Franco

2017-07-01

Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

The effects of L-arginine, alone and combined with vitamin C, on mineral status in relation to its antidiabetic, anti-inflammatory, and antioxidant properties in male rats on a high-fat diet.

PubMed

Suliburska, Joanna; Bogdanski, Paweł; Krejpcio, Zbigniew; Pupek-Musialik, Danuta; Jablecka, Anna

2014-01-01

The aim of this study was to evaluate the influence of the intake of L-arginine alone and of L-arginine with vitamin C on mineral concentration in rats fed with a high-fat diet, and to assess the lipid glucose, insulin, and total antioxidant status (TAS) and tumor necrosis factor (TNF) alpha serum levels that result. Wistar rats were assigned to groups fed with either a standard control diet (C), a diet high in fat (FD), a diet high in fat with L-arginine, or a diet high in fat with L-arginine and vitamin C. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The liver, spleen, kidneys, pancreas, heart, and gonads were collected, as were blood samples. The total serum cholesterol, triglyceride, fasting glucose, insulin, TAS, and TNF alpha levels were measured. The tissue calcium, magnesium, iron, zinc, and copper concentrations were determined. It was found that L-arginine supplementation diminished the effect of the modified diet on the concentration of iron in the liver and spleen and of copper in heart. At the same time, it was observed that L-arginine supplementation reduced the effect of the high-fat diet on insulin, TNF alpha, and TAS. The combination of L-arginine and vitamin C produced a similar effect on the mineral levels in the tissues as did L-arginine used alone. Moreover, positive correlations between serum insulin and iron in the liver, between TNF alpha and iron in the liver, and between TNF alpha and copper in the heart were observed. The level of TAS in serum was inversely correlated with the copper level in the heart and the iron level in the liver. We concluded that the beneficial influence of L-arginine on insulin, TAS, and TNF alpha serum level is associated with changes in the iron and copper status in rats fed with a high-fat diet. No synergistic effect of L-arginine and vitamin C in the biochemical parameters or in the mineral status in rats fed with the modified diet was observed.

Intralesional copper wire retention and pingyangmycin injection: an effective combinational therapy for complex venous malformation in soft tissue.

PubMed

Yuan, S-M; Hong, Z-J; Jiang, H-Q; Wang, J; Hu, X-B

2014-04-01

Complex venous malformations (VMs) may extensively involve the soft tissue. The treatment remains a challenge till now. Here we introduce a combinational therapy of copper wires and pingyangmycin (bleomycin A5,PYM). Copper wires were retained in VMs by repeated penetration with a straight needle. Subsequently, PYM solution was injected into the lesion. Eight to 10 days later, copper wires were removed. The dressing was changed every day until the puncture pores healed. Magnetic resonance imaging scanning was performed to observe the change of VMs. From January 2001 to December 2011, 56 patients were treated. During the follow-up period, most of the VMs shrunk obviously. The symptoms were relieved or disappeared. The complications included local pain, temporary paraesthesia and moderate fever, which disappeared quickly after the removal of copper wires. This combinational therapy is a safe and effective approach for the complex VMs in soft tissue.

Effect of pomegranate (Punica granatum L.) juice on kidney, liver, heart and testis histopathological changes, and the tissues lipid peroxidation and antioxidant status in lead acetate-treated rats.

PubMed

Aksu, D S; Sağlam, Y S; Yildirim, S; Aksu, T

2017-10-31

Pomegranate juice (PJ) contains relevant amounts of active biological compounds which alleviate the detrimental effects of chronic heavy metal exposure. This study investigated the protective potential of PJ against lead-induced oxidative stress. A total of forty adult male Sprague Dawley rats were divided into four experimental groups. The animals were fed a standard pellet diet and tap water ad libitum. The rats were divided into four groups (n=10 for each group): control, lead asetat (2000 ppm), low-treated PJ- a daily dose of 2.000 ppm lead plus 30µl pomegranate juice (included 1.050 µmol total polyphenols, gallic acid equivalent), and high-treated PJ- a daily dose of 2.000 ppm lead plus 60µl pomegranate juice (included 2.100 µmol total polyphenols, gallic acid equivalent). The treatments were delivered for 5 weeks. After the treatment period, the tissues samples (kidney, liver, heart and testis) were collected. Tissue lead (Pb) and mineral amounts (copper, zinc, and iron), tissues lipid peroxidation level and antioxidant status, and tissues histopathological changes were determined. The results showed that the highest rate lead loading was in the kidney and the testis. Pomegranate juice was decreased the lead levels of soft tissues examined; increased Zn amounts in tissues of which the lead accumulation was higher (kidney and the testis); decreased the copper, zinc and the iron levels of the liver and heart tissues, without creating a weakness in antioxidant capacity of these tissues, restricted the oxidative stress by decreasing lipid peroxidation, improved both of the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalaz (CAT), and the level of glutathione (GSH) in all the tissues examined in lead-treated groups. As histopathological findings, the cellular damage induced by lead in the tissues of the kidney, liver and the heart were observed to have been partially prevented by PJ treatment. The protective effect of PJ was more pronounced in the testis compared to those others.

Citric acid assisted phytoremediation of copper by Brassica napus L.

PubMed

Zaheer, Ihsan Elahi; Ali, Shafaqat; Rizwan, Muhammad; Farid, Mujahid; Shakoor, Muhammad Bilal; Gill, Rafaqa Ali; Najeeb, Ullah; Iqbal, Naeem; Ahmad, Rehan

2015-10-01

Use of organic acids for promoting heavy metals phytoextraction is gaining worldwide attention. The present study investigated the influence of citric acid (CA) in enhancing copper (Cu) uptake by Brassica napus L. seedlings. 6 Weeks old B. napus seedlings were exposed to different levels of copper (Cu, 0, 50 and 100µM) alone or with CA (2.5mM) in a nutrient medium for 40 days. Exposure to elevated Cu levels (50 and 100µM) significantly reduced the growth, biomass production, chlorophyll content, gas exchange attributes and soluble proteins of B. napus seedlings. In addition, Cu toxicity increased the production of hydrogen peroxide (H2O2), malondialdehyde (MDA) and electrolyte leakage (EL) in leaf and root tissues of B. napus. Activities of antioxidant enzymes such as guaiacol peroxidase (POD), superoxide dismutase (SOD), catalases (CAT), ascorbate peroxidase (APX) in root and shoot tissues of B. napus were increased in response to lower Cu concentration (50µM) but increased under higher Cu concentration (100µM). Addition of CA into nutrient medium significantly alleviated Cu toxicity effects on B. napus seedlings by improving photosynthetic capacity and ultimately plant growth. Increased activities of antioxidant enzymes in CA-treated plants seems to play a role in capturing of stress-induced reactive oxygen species as was evident from lower level of H2O2, MDA and EL in CA-treated plants. Increasing Cu concentration in the nutrient medium significantly increased Cu concentration in in B. napus tissues. Cu uptake was further increased by CA application. These results suggested that CA might be a useful strategy for increasing phytoextraction of Cu from contaminated soils. Copyright © 2015 Elsevier Inc. All rights reserved.

Copper Contamination Impairs Herbivore Initiation of Seaweed Inducible Defenses and Decreases Their Effectiveness

PubMed Central

2015-01-01

Seaweed-herbivore interactions are often mediated by environmental conditions, yet the roles of emerging anthropogenic stressors on these interactions are poorly understood. For example, chemical contaminants have unknown consequences on seaweed inducible resistance and herbivore response to these defenses despite known deleterious effects of contaminants on animal inducible defenses. Here, we investigated the effect of copper contamination on the interactions between a snail herbivore and a brown seaweed that displays inducible resistance to grazing. We examined seaweed inducible resistance and its effectiveness for organisms exposed to copper at two time points, either during induction or after herbivores had already induced seaweed defenses. Under ambient conditions, non-grazed tissues were more palatable than grazed tissues. However, copper additions negated the preference for non-grazed tissues regardless of the timing of copper exposure, suggesting that copper decreased both how herbivores initiated these inducible defenses and their subsequent effectiveness. Copper decreased stimulation of defenses, at least in part, by suppressing snail grazing pressure—the cue that turns inducible defenses on. Copper decreased effectiveness of defenses by preventing snails from preferentially consuming non-grazed seaweed. Thus, contaminants can potentially stress communities by changing seaweed-herbivore interactions mediated via inducible defenses. Given the ubiquity of seaweed inducible resistance and their potential influence on herbivores, we hypothesize that copper contamination may change the impact of these resistant traits on herbivores. PMID:26274491

Release of copper from embedded solid copper bullets into muscle and fat tissues of fallow deer (Dama dama), roe deer (Capreolus capreolus), and wild boar (Sus scrofa) and effect of copper content on oxidative stability of heat-processed meat.

PubMed

Schuhmann-Irschik, I; Sager, M; Paulsen, P; Tichy, A; Bauer, F

2015-10-01

When venison with embedded copper bullets was subjected to different culinary processing procedures, the amount of copper released from the embedded bullet was affected more by the retention period of the bullet in the meat during cool storage, than by the different heating protocols. The presence of copper fragments had no significant effect on levels of thiobarbituric acid reactive substances (TBARS). Conversely, TBARS in lean meat (fallow deer, wild boar, roe deer) were significantly affected by culinary treatment (higher TBARS in boiled and boiled-stored meat than in meat barbecued or boiled in brine). In pork-beef patties doped with up to 28mg/kg Cu, TBARS increased after dry-heating and subsequently storing the meat patties. The amount of copper doping had no effect on TBARS for 0 and 7days of storage, but a significant effect at day 14 (fat oxidation retarded at higher Cu doses). Evidence is presented that wild boar meat may be more sensitive to fat oxidation than pork-beef. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concentrations of metals in tissues of lowbush blueberry (Vaccinium angustifolium) near a copper-nickel smelter at Sudbury, Ontario, Canada: A factor analytic approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bagatto, G.; Shorthouse, J.D.; Crowder, A.A.

1993-10-01

Ecosystems damaged by emissions from the copper-nickel smelters of Inco and Falconbridge Ltd. near Sudbury, Ontario, Canada have provided a unique opportunity to study the effects of metal particulates and sulphur dioxide fumigations on plant and animal communities. The most infamous terrain in the Sudbury region is nearest the smelters (two active and one closed), where nearly all vegetation has been destroyed and soils eroded and contaminated. However, over all the past twenty years, some species of plants have developed a tolerance to polluted soils and some denuded lands have been naturally and artificially revegetated. Furthermore, a series of uniquemore » anthropogenic forests have developed away from the smelters. Several studies on the accumulation of metals in plant tissues indicate the levels of metals are usually highest closest to the smelters. Consequently, several studies have reported high correlations between plant concentrations of certain metals with distance from the source of pollution. However, tissue metal burdens are not always correlated with distance from the emission source, suggesting that other biological and physico-chemical factors may influence tissue metal burdens in the Sudbury habitat. The present study provides information on the metal burdens in another plant, lowbush blueberry, growing both near and away from the smelters. This study assesses the apparent influence of the Sudbury smelting operations on plant tissue burdens of five additional elements, along with copper and nickel, by using a factor analytic approach. This approach will allow determination of underlying factors which govern tissue metal burdens in a polluted environment and helps to refine the future direction of research in the Sudbury ecosystem. 12 refs., 2 tabs.« less

Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.

PubMed

Genc, Gizem Esra; Ozturk, Zeynep; Gumuslu, Saadet; Kupesiz, Alphan

2016-03-01

The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.

[The direct AAS determination of micro elements in hair and nail by base-digestion].

PubMed

Ju, Hong-fang

2002-08-01

The study of micro elements is more and more extensively, and people can gain some informations by the level of micro elements in tissue. This paper tempts to dissolve hair or nail in 2 mol.L-1 NaOH and determinate nine micro elements including calcium, zinc, iron, manganese, nickel, cadmium, copper, lead and bismuth in them by base-digestion with FAAS and GFAAS. It shows that the measured value of these elements is coincident with reference articles reported, except bismuth. The elements' percent recoveries are 90.0%-110.8%. The result also shows that the level of zinc and copper in hair are higher than in nail, and the level of bismuth, cadmium and iron in hair are lower than in nail, but the level of micro elements in hair and in nail are not correlative.

[Wilsons disease].

PubMed

Mareček, Z; Brůha, R

2013-07-01

Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilsons disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilsons disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The dia-gnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, KayserFleischer ring). The dia-gnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilsons disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.

Heavy metal concentrations in commercial deep-sea fish from the Rockall Trough

NASA Astrophysics Data System (ADS)

Mormede, S.; Davies, I. M.

2001-05-01

Samples of monkfish ( Lophius piscatorius), black scabbard ( Aphanopus carbo), blue ling ( Molva dypterygia), blue whiting ( Micromesistius poutassou) and hake ( Merluccius merluccius) were obtained from 400 to 1150 m depth on the continental slope of Rockall Trough west of Scotland. Muscle, liver, gill and gonad tissue were analysed for arsenic, cadmium, copper, lead, mercury and zinc by various atomic absorption techniques. Median concentrations of arsenic in the muscle tissue ranged from 1.25 to 8.63 mg/kg wet weight; in liver tissue from 3.04 to 5.72 mg/kg wet weight; cadmium in muscle tissue from <0.002 to 0.034 mg/kg wet weight, in liver tissue from 0.11 to 6.98 mg/kg wet weight; copper in the muscle from 0.12 to 0.29 mg/kg wet weight, in the liver from 3.47 to 11.87 mg/kg wet weight; lead levels in muscle from <0.002 to 0.009 mg/kg wet weight, respectively, and in liver tissue <0.05 mg/kg wet weight for all species. In general, the concentrations are similar to those previously published on deep-sea fish, and higher or similar to those published for shallow water counterparts. All metal levels in black scabbard livers are much higher than in the other fish, and between 2 and 30 times higher than the limits of the European Dietary Standards and Guidelines. Differences in accumulation patterns between species and elements, as well as between organs are described using univariate and multivariate statistics (scatterplots, discriminant analysis, triangular plots).

Copper toxicity in ruminant animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oehme, F.W.

This discussion includes clinical and post mortem features, metabolism of both normal and toxic quantities of copper, effect of copper upon the tissues, and control treatment and prevention of copper toxicity. These effects are discussed in regard to ruminants. Specific emphasis is placed on metabolism and biochemistry. 33 references, 3 figures.

Survey of heavy metals in internal tissues of Great cormorant collected from southern wetlands of Caspian Sea, Iran.

PubMed

Aazami, Jaber; KianiMehr, Naser

2017-12-29

The level of mercury, iron, copper, and zinc was measured in 18 Great cormorants (Phalacrocorax carbo) collected from Anzali and Gomishan wetlands in the south of the Caspian Sea. The mean level of metals in dried tissues of the muscle, liver, and kidney was 2.26, 5.71, 3.79-Hg; 943.54, 379.97, 348.05-Fe; 42.64, 14.78, 60.79-Cu, and 71.97, 134.63, 77.82-Zn, respectively (mg/kg). There was no significant different between genders in terms of accumulation of metals, except for copper in the kidney. The results of Pearson correlation showed a positive and strong relationship between the fat in the liver and mercury (r = 0.95, R 2  = 0.90). Also, there was a significant difference between the values of all metals with the allowable limits presented in EPA, WHO, and CCME, where all of values were above standard levels. Thus, as the muscles of the bird are sometimes eaten by humans, this result is a serious warning. Nevertheless, the relatively high levels of heavy metals accumulated in different tissues of Great cormorant at that time are a result of their high weight and nourishment they have at the terminal days of their migration due to lack of natural physical activity. Regarding to the importance of heavy metals in birds, we suggest the same study to be conducted on the species in other seasons and wetlands.

Deposition of corrosion products from dowels on human dental root surfaces measured with proton microprobe technique

NASA Astrophysics Data System (ADS)

Brune, D.; Brunell, G.; Lindh, U.

1982-06-01

Distribution of copper, mercury and zinc on human teeth root surfaces adjacent to dowels of gold alloy or brass as well as dowels of brass in conjunction with an amalgam crown has been measured with a proton microprobe using PIXE techniques. Upper limits of the contents of gold and silver on the root surfaces were established. Pronounced concentration profiles of copper and zinc were observed on the root surfaces of teeth prepared with dowels of brass. The dowel of gold alloy revealed only zinc deposition. The major part of copper on the root surfaces is assumed to arise from corrosion of the dowels, and has been transported to the surface by diffusion through the dential tubuli. Zinc in the volume analysed is a constituent of dentin tissue as well as a corrosion product of the brass dowel. Part of the zinc level could also be ascribed to erosion of the zinc phosphate cement matrix. The volumes analysed were (25×25×25)μm 3. The levels of copper, mercury and zinc on the tooth root surfaces attained values up to about 200, 20 and 600 ppm, respectively.

Copper sulphate (CuSO4) toxicity on tissue phosphatases activity and carbohydrates turnover in Achatina fulica.

PubMed

Ramalingam, K; Indra, D

2002-04-01

A time course study on the sublethal toxicity of CuSO4 on tissue carbohydrate metabolites level and their phosphatases activity in Achatina fulica revealed differential response. The levels of total carbohydrates and glycogen in the body mass muscle, foot muscle and hemolymph revealed their involvement in the endogenous derivation of energy during stress. The same metabolites in digestive gland revealed its importance to reproduction and development. The lactate accumulated in all the tissues implied the mechanism of CuSO4 toxicosis in the metabolic acidosis. The decrease of pyruvate in foot muscle, body mass muscle and hemolymph inferred the preponderance of glycolysis in energy derivation. In contrast, the pyruvate concentration in digestive gland revealed its differential response in the stress metabolic sequence of changes, as a unique tissue. The lactate/pyruvate ratio and the calcium content in tissues constitute direct evidences for the snails adaptation to toxic stress.

A 37-year-old Menkes disease patient-Residual ATP7A activity and early copper administration as key factors in beneficial treatment.

PubMed

Tümer, Z; Petris, M; Zhu, S; Mercer, J; Bukrinski, J; Bilz, S; Baerlocher, K; Horn, N; Møller, L B

2017-11-01

Menkes disease (MD) is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving MD patient (37 years) receiving early-onset and long-term copper treatment. He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared. These findings suggest that some cuproenzymes maintain their function when sufficient copper is provided to the cells; and underline the importance of early initiated copper treatment, efficiency of which is likely to be dependent on the mutant ATP7A function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biochemical response of the mussel Mytilus coruscus (Mytiloida: Mytilidae) exposed to in vivo sub-lethal copper concentrations

NASA Astrophysics Data System (ADS)

Li, Yifeng; Gu, Zhongqi; Liu, Hong; Shen, Heding; Yang, Jinglong

2012-09-01

Many aquatic organisms are negatively affected by exposure to high copper concentrations. We investigated the biochemical response of the mussel Mytilus coruscus (Mytiloida: Mytilidae) to copper exposure. In vivo bioassays using M. coruscus and different copper concentrations were conducted. The activity of six biomarkers, namely superoxide dismutase (SOD), catalase (CAT), acid phosphatase (ACP), alkaline phosphatase (AKP), glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) were measured. Survival rates decreased with increased copper concentrations and exposure times. The LC50 values at 48, 72, and 96 h exposure were 0.48, 0.37, and 0.32 mg/L, respectively. Within digestive glands, CAT activity increased with increasing Cu concentrations. The activity of AKP showed no significant change, while the remaining four enzymes showed decreasing activity with increasing Cu concentrations. Within the gills, AKP activity increased when the Cu concentration was 0.05 mg/L, but showed no significant changes at higher concentrations. Activity of CAT and ACP within gills tended to decrease with increasing Cu concentration. The activity of SOD and GPT decreased at an exposure concentration of 0.2 mg/L. GOT activity within gills decreased at 0.1 mg/L and increased at an exposure concentration of 0.2 mg/L. Within the adductor muscle, AKP activity increased at 0.05 mg/L but did not change at higher exposure concentrations. ACP activity within adductor muscle tissue showed no change, while activities of CAT, GOT and GPT decreased with increasing Cu concentrations. SOD activity within the adductor muscle tissue significantly decreased at the 0.02, 0.05 and 0.2 mg/L exposure concentrations. Our results show tissue specific differences for the six biomarkers in for M. coruscus. Our findings provide the basis for the establishment of reference activity levels against which biomarker changes can be estimated, and are essential preliminary steps in development of in vivo bioassays.

Tissue Trace Elements and Lipid Peroxidation in Breeding Female Bank Voles Myodes glareolus.

PubMed

Bonda-Ostaszewska, Elżbieta; Włostowski, Tadeusz; Łaszkiewicz-Tiszczenko, Barbara

2018-04-27

Recent studies have demonstrated that reproduction reduces oxidative damage in various tissues of small mammal females. The present work was designed to determine whether the reduction of oxidative stress in reproductive bank vole females was associated with changes in tissue trace elements (iron, copper, zinc) that play an essential role in the production of reactive oxygen species. Lipid peroxidation (a marker of oxidative stress) and iron concentration in liver, kidneys, and skeletal muscles of reproducing bank vole females that weaned one litter were significantly lower than in non-reproducing females; linear regression analysis confirmed a positive relation between the tissue iron and lipid peroxidation. The concentrations of copper were significantly lower only in skeletal muscles of reproductive females and correlated positively with lipid peroxidation. No changes in tissue zinc were found in breeding females when compared with non-breeding animals. These data indicate that decreases in tissue iron and copper concentrations may be responsible for the reduction of oxidative stress in reproductive bank vole females.

Transcranial Red and Near Infrared Light Transmission in a Cadaveric Model

PubMed Central

Jagdeo, Jared R.; Adams, Lauren E.; Brody, Neil I.; Siegel, Daniel M.

2012-01-01

Background and Objective Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model. Study Design/Materials and Methods To investigate this idea, we measured the transmission of near infrared light energy, using red light for purposes of comparison, through intact cadaver soft tissue, skull bones, and brain using a commercially available LED device at 830 nm and 633 nm. Results Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions. Conclusion These findings indicate that near infrared light can penetrate formalin fixed soft tissue, bone and brain and implicate that benefits observed in clinical studies are potentially related to direct action of near infrared light on neural tissue. PMID:23077622

Studies on Zinc and Copper Ion in Relation to Wound Healing in Male and Female West African Dwarf Goats.

PubMed

Olaifa, A K; Fadason, S T

2017-03-06

Wound healing remains a challenging clinical problem for which precise and efficient management is essential in order to curtail morbidity and mortality. Wound healing has been shown to depend upon the availability of appropriate trace elements like copper and zinc which serve as enzyme cofactors and structural components in tissue repair. This study aims at evaluating the distribution of zinc and copper found in the hair as well as skin during epidermal wound healing. Adult and healthy West African dwarf (WAD) goats of both sexes fed with concentrate, grass, cassava peel and water ad libitum were used. The animals were housed for three weeks before commencement of the experiments. Epidermal wounds were created on the trunks of all the goats using cardboard template of 1cm². Progressive changes in wound contraction were monitored grossly by placing clean and sterile venier calliper on the wound margin. Hair and skin elemental (copper and zinc) analyses were done using atomic absorption spectroscopy (AAS). Significant increases in Cu level were observed in the female hair compared with that of males. There were significant increases in the Zn levels of the females' hair compared with the males. The wound healed faster in female goat compared with the males. The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals. The pattern of distribution between zinc and copper concentration in the skin and hair of the male and female goats observed in this study could be added factor responsible for early wound healing in female. Therefore, our findings suggest that the distribution in the Cu and Zinc level in skin and hair of both male and female goats could also be a factor for wound healing in the animals.

Simulations to Evaluate Accuracy and Patient Dose in Neutron-Stimulated, Emission-Computed Tomography (NSECT) for Diagnosis of Breast Cancer

DTIC Science & Technology

2008-04-01

tissues , Cancer 52 (3) (1983) 508. [18] J.O. Ogunlewe, D.N. Osegbe, Zinc and cadmium concentrations in indigenous blacks with normal, hypertrophic...142 (1976) 65. [10] E.J. Margalioth, J.G. Schenker, M. Chevion, Copper and zinc levels in normal and malignant tissues , Cancer 52 (5) (1983) 868. [11...Krajewska, Zinc and cadmium analysis in human prostate neoplasms, Biol. Trace Elem. Res. 59 (1–3) (1997) 145. [22] V.Y. Zaichick, T.V. Sviridova

Rapid and reliable diagnosis of Wilson disease using X-ray fluorescence.

PubMed

Kaščáková, Slávka; Kewish, Cameron M; Rouzière, Stéphan; Schmitt, Françoise; Sobesky, Rodolphe; Poupon, Joël; Sandt, Christophe; Francou, Bruno; Somogyi, Andrea; Samuel, Didier; Jacquemin, Emmanuel; Dubart-Kupperschmitt, Anne; Nguyen, Tuan Huy; Bazin, Dominique; Duclos-Vallée, Jean-Charles; Guettier, Catherine; Le Naour, François

2016-07-01

Wilson's disease (WD) is a rare autosomal recessive disease due to mutations of the gene encoding the copper-transporter ATP7B. The diagnosis is hampered by the variability of symptoms induced by copper accumulation, the inconstancy of the pathognomonic signs and the absence of a reliable diagnostic test. We investigated the diagnostic potential of X-ray fluorescence (XRF) that allows quantitative analysis of multiple elements. Studies were performed on animal models using Wistar rats (n = 10) and Long Evans Cinnamon (LEC) rats (n = 11), and on human samples including normal livers (n = 10), alcohol cirrhosis (n = 8), haemochromatosis (n = 10), cholestasis (n = 6) and WD (n = 22). XRF experiments were first performed using synchrotron radiation to address the elemental composition at the cellular level. High-resolution mapping of tissue sections allowed measurement of the intensity and the distribution of copper, iron and zinc while preserving the morphology. Investigations were further conducted using a laboratory X-ray source for irradiating whole pieces of tissue. The sensitivity of XRF was highlighted by the discrimination of LEC rats from wild type even under a regimen using copper deficient food. XRF on whole formalin-fixed paraffin embedded needle biopsies allowed profiling of the elements in a few minutes. The intensity of copper related to iron and zinc significantly discriminated WD from other genetic or chronic liver diseases with 97.6% specificity and 100% sensitivity. This study established a definite diagnosis of Wilson's disease based on XRF. This rapid and versatile method can be easily implemented in a clinical setting.

Multi-biofunctional polymer graphene composite for bone tissue regeneration that elutes copper ions to impart angiogenic, osteogenic and bactericidal properties.

PubMed

Jaidev, L R; Kumar, Sachin; Chatterjee, Kaushik

2017-11-01

Despite several recent advances, poor vascularization in implanted scaffolds impedes complete regeneration for clinical success of bone tissue engineering. The present study aims to develop a multi-biofunctional nanocomposite for bone tissue regeneration using copper nanoparticle decorated reduced graphene oxide (RGO_Cu) hybrid particles in polycaprolactone (PCL) matrix (PCL/RGO_Cu). X-ray photoelectron spectroscopy and X-ray diffraction confirmed the presence of copper oxides (CuO and Cu 2 O) on RGO. Thermogravimetric analysis showed that 11.8% of copper was decorated on RGO. PCL/RGO_Cu exhibited steady release of copper ions in contrast to burst release from the composite containing copper alone (PCL/Cu). PCL/RGO_Cu exhibited highest modulus due to enhanced filler exfoliation. Endothelial cells rapidly proliferated on PCL/RGO_Cu confirming cytocompatibility. The sustained release of ions from PCL/RGO_Cu composites augmented tube formation by endothelial cells evidenced enhanced angiogenic activity. Gene expression of angiogenic markers VEGF and ANG-2 was higher on PCL/RGO_Cu compared to PCL. The osteogenic activity of PCL/RGO_Cu was confirmed by the 87% increase in mineral deposition by pre-osteoblasts compared to PCL. The bactericidal activity of PCL/RGO_Cu showed 78% reduction in viability of Escherichia coli. Thus, the multi-biofunctional PCL/RGO_Cu composite exhibits angiogenic, osteogenic and bactericidal properties, a step towards addressing some of the critical challenges in bone tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Accumulation and hyperaccumulation of copper in plants

NASA Astrophysics Data System (ADS)

Adam, V.; Trnkova, L.; Huska, D.; Babula, P.; Kizek, R.

2009-04-01

Copper is natural component of our environment. Flow of copper(II) ions in the environment depends on solubility of compounds containing this metal. Mobile ion coming from soil and rocks due to volcanic activity, rains and others are then distributed to water. Bio-availability of copper is substantially lower than its concentration in the aquatic environment. Copper present in the water reacts with other compounds and creates a complex, not available for organisms. The availability of copper varies depending on the environment, but moving around within the range from 5 to 25 % of total copper. Thus copper is stored in the sediments and the rest is transported to the seas and oceans. It is common knowledge that copper is essential element for most living organisms. For this reason this element is actively accumulated in the tissues. The total quantity of copper in soil ranges from 2 to 250 mg / kg, the average concentration is 30 mg / kg. Certain activities related to agriculture (the use of fungicides), possibly with the metallurgical industry and mining, tend to increase the total quantity of copper in the soil. This amount of copper in the soil is a problem particularly for agricultural production of food. The lack of copper causes a decrease in revenue and reduction in quality of production. In Europe, shows the low level of copper in total 18 million hectares of farmland. To remedy this adverse situation is the increasing use of copper fertilizers in agricultural soils. It is known that copper compounds are used in plant protection against various illnesses and pests. Mining of minerals is for the development of human society a key economic activity. An important site where the copper is mined in the Slovakia is nearby Smolníka. Due to long time mining in his area (more than 700 years) there are places with extremely high concentrations of various metals including copper. Besides copper, there are also detected iron, zinc and arsenic. Various plant species have adapted on such stress. The aim of this study is to investigate the behaviour of copper in plants and to assess its potential effect on the surrounding environment. To detect copper in biological samples electrochemical methods were employed particularly differential pulse voltammetry (DPV). Copper gave signals at 0.02 V measured by DPV. The obtained calibration dependence was linear (R2 = 0.995). Further, this method was utilized for determination of copper in real soil samples obtained from previously mentioned heavy-metal-polluted mining area. The content varied within range from tens to hundreds of mg of copper per kg of the soil. Moreover, we focused on investigation of copper influence on seedlings of Norway spruce. The seedlings were treated with copper (0, 0.1, 10 and 100 mM) for four weeks. We observed anatomical-morphological changes and other biochemical parameters in plants. We determined that seedlings synthesized more than 48 % protective thiols (glutathione and phytochelatins) compared to control ones. We investigated copper distribution in plant tissues by diphenylcarbazide staining. We found out that copper is highly accumulated in parenchymal stalk cells. In needles, change in auto-fluorescence of parenchymal cells of mesoderm similarly to endodermis cells. Besides, we analyzed samples of plants from the polluted area (spruce, pin, birch). The data obtained well correlated with previously mentioned. Acknowledgement The work on this experiment was supported by grant: INCHEMBIOL MSM0021622412.

Ecological-Evaluation of Organotin-Contaminated Sediment.

DTIC Science & Technology

1985-07-01

the potential for bioaccumulation of cadmium, chromium, copper, mercury , silver, pesticides, PCBs, petroleum hydrocarbons, and organotins RESULTS The...tissues were frozen for subsequent bioaccumulation estimates. Tissues and sediment samples were analyzed for cadmium, chromium, copper, mercury , silver...spectroscopy; mercury was analyzed by cold vapor atomic absorption spectroscopy. Pesticides, PCBs, and petroleum hydrocarbons were measured by gas

Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: A potential role in cancer chemoprevention.

PubMed

Arif, Hussain; Sohail, Aamir; Farhan, Mohd; Rehman, Ahmed Abdur; Ahmad, Aamir; Hadi, S M

2018-01-01

Flavonoids, a class of polyphenols are known to be effective inducers of apoptosis and cytotoxicity in cancer cells. It is believed that antioxidant activity of polyphenols cannot fully account for induction of apoptosis and chemotherapeutic prevention in various cancers. In this article, by employing single cell alkaline gel electrophoresis (comet assay), we established that antioxidants, flavonoids such as (myricetin=MN, fisetin=FN, quercetin=QN, kaempferol=KL and galangin=GN) can cause cellular DNA breakage, also act as pro-oxidant in presence of transition metal ion such as copper. It was observed that the extent of cellular DNA breakage was found significantly higher in presence of copper. Hydroxyl radicals are generated as a sign of flavonoids' pro-oxidant nature through redox recycling of copper ions. Further, a dose-dependent inhibition of proliferation of breast cancer cells MDA-MB-231 by MN was found leading to pro-oxidant cell death, as assessed by MTT assay. Since levels of copper are considerably elevated in tissue, cell and serum during various malignancies, suggesting that cancer cells would be more subject to copper induced oxidative DNA breakage. Such a copper dependent pro-oxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental contaminants in tissues, foods, and feces of California condors

USGS Publications Warehouse

Wiemeyer, Stanley N.; Krynitsky, A.J.; Wilbur, S.R.; Wilbur, Sanford R.; Jackson, Jerome A.

1983-01-01

Two wild California Condors contained moderate to high levels of DDE in their tissues. The levels found could be high enough to cause reproductive problems in adult condors, if the assumption is made that condors are as susceptible to DDE as many other species of birds of prey. Other organochlorines occurred at low levels and probably were not high enough to cause deleterious effects. Metal residues in tissues of one bird were generally low except for copper in liver and lead in bone. Normal background levels of these metals in cathartids are unknown, making interpretation of the results difficult. Organochlorine residues in biopsy samples from a captive condor were low and probably would not have an adverse effect on reproduction if the bird were used for captive breeding. Organochlorines were not detected in food items used in the supplemental feeding program, and mercury and lead residues in these items were generally low. Information is needed on current contaminant levels in natural condor prey throughout the condor range.

Basal ganglia dysfunction

MedlinePlus

... disease Metabolic problems Multiple sclerosis (MS) Poisoning with copper, manganese, or other heavy metals Stroke Tumors A ... the brain) Wilson disease (disorder causing too much copper in the body's tissues)

Metabolic changes of Vitis vinifera berries and leaves exposed to Bordeaux mixture.

PubMed

Martins, Viviana; Teixeira, António; Bassil, Elias; Blumwald, Eduardo; Gerós, Hernâni

2014-09-01

Since the development of Bordeaux mixture in the late 1800's, copper-based fungicides have been widely used against grapevine (Vitis vinifera L.) diseases, mainly in organic but also in conventional viticulture; however their intensive use has raised phytotoxicity concerns. In this study, the composition of grape berries and leaves upon Bordeaux mixture treatment was investigated during the fructification season by a metabolomic approach. Four applications of Bordeaux mixture till 3 weeks before harvest were performed following the regular management practices of organic viticulture. Results showed that the copper-based treatment affected the content in sugars, organic acids, lipids and flavan-3-ols of grapes and leaves at specific developmental stages. Nonetheless, the levels of sucrose, glucose and fructose, and of tartaric and malic acids were not significantly affected in mature grapes. In contrast, a sharp decrease in free natural amino acids was observed, together with a reduction in protein content and in mineral nitrogen forms. The treatment with Bordeaux mixture increased by 7-fold the copper levels in tissue extracts from surface-washed mature berries. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease.

PubMed

Cooper, Garth J S

2011-07-09

This article reviews recent evidence, much of which has been generated by my group's research programme, which has identified for the first time a previously unknown copper-overload state that is central to the pathogenesis of diabetic organ damage. This state causes tissue damage in the blood vessels, heart, kidneys, retina and nerves through copper-mediated oxidative stress. This author now considers this copper-overload state to provide an important new target for therapeutic intervention, the objective of which is to prevent or reverse the diabetic complications. Triethylenetetramine (TETA) has recently been identified as the first in a new class of anti-diabetic molecules through the original work reviewed here, thus providing a new use for this molecule, which was previously approved by the US FDA in 1985 as a second-line treatment for Wilson's disease. TETA acts as a highly selective divalent copper (Cu(II)) chelator that prevents or reverses diabetic copper overload, thereby suppressing oxidative stress. TETA treatment of diabetic animals and patients has identified and quantified the interlinked defects in copper metabolism that characterize this systemic copper overload state. Copper overload in diabetes mellitus differs from that in Wilson's disease through differences in their respective causative molecular mechanisms, and resulting differences in tissue localization and behaviour of the excess copper. Elevated pathogenetic tissue binding of copper occurs in diabetes. It may well be mediated by advanced-glycation endproduct (AGE) modification of susceptible amino-acid residues in long-lived fibrous proteins, for example, connective tissue collagens in locations such as blood vessel walls. These AGE modifications can act as localized, fixed endogenous chelators that increase the chelatable-copper content of organs such as the heart and kidneys by binding excessive amounts of catalytically active Cu(II) in specific vascular beds, thereby focusing the related copper-mediated oxidative stress in susceptible tissues. In this review, summarized evidence from our clinical studies in healthy volunteers and diabetic patients with left-ventricular hypertrophy, and from nonclinical models of diabetic cardiac, arterial, renal and neural disease is used to construct descriptions of the mechanisms by which TETA treatment prevents injury and regenerates damaged organs. Our recent phase II proof-of-principle studies in patients with type 2 diabetes and in nonclinical models of diabetes have helped to define the pathogenetic defects in copper regulation, and have shown that they are reversible by TETA. The drug tightly binds and extracts excess systemic Cu(II) into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency, even after prolonged use. Its physicochemical properties, which are pivotal for its safety and efficacy, clearly differentiate it from all other clinically available transition metal chelators, including D-penicillamine, ammonium tetrathiomolybdate and clioquinol. The studies reviewed here show that TETA treatment is generally effective in preventing or reversing diabetic organ damage, and support its ongoing development as a new medicine for diabetes. Trientine (TETA dihydrochloride) has been used since the mid-1980s as a second-line treatment for Wilson's disease, and our recent clinical studies have reinforced the impression that it is likely to be safe for long-term use in patients with diabetes and related metabolic disorders. There is substantive evidence to support the view that diabetes shares many pathogenetic mechanisms with Alzheimer's disease and vascular dementia. Indeed, the close epidemiological and molecular linkages between them point to Alzheimer's disease/vascular dementia as a further therapeutic target where experimental pharmacotherapy with TETA could well find further clinical application.

Concentrations of selected trace elements in fish tissue and streambed sediment in the Clark Fork-Pend Oreille and Spokane River basins, Washington, Idaho, and Montana, 1998

USGS Publications Warehouse

Maret, Terry R.; Skinner, K.D.

2000-01-01

Fish tissue and bed sediment samples were collected from 16 stream sites in the Northern Rockies Intermontane Basins study area in 1998 as part of the U.S. Geological Survey National Water-Quality Assessment Program. Bed sediment samples were analyzed for 45 trace elements, and fish livers and sportfish fillets were analyzed for 22 elements to characterize the occurrence and distribution of these elements in relation to stream characteristics and land use activities. Nine trace elements of environmental concern—arsenic, cadmium, chromium, copper, lead, mercury, nickel, selenium, and zinc—were detected in bed sediment, but not all of these elements were detected in fish tissue. Trace-element concentrations were highest in bed sediment samples collected at sites downstream from significant natural mineral deposits and (or) mining activities. Arsenic, cadmium, copper, lead, mercury, and zinc in bed sediment at some sites were elevated relative to national median concentrations, and some concentrations were at levels that can adversely affect aquatic biota. Although trace-element concentrations in bed sediment exceeded various guidelines, no concentrations in sportfish fillets exceeded U.S. Environmental Protection Agency screening values for the protection of human health. Correlations between most trace-element concentrations in bed sediment and fish tissue (liver and fillet) were not significant (r0.05). Concentrations of arsenic, cadmium, copper, lead, mercury, nickel, selenium, and zinc in bed sediment were significantly correlated (r=0.53 to 0.88, p2=0.95 and 0.99, p<0.001) that corresponded to trace-element enrichment categories. These strong relations warrant further study using mine density as an explanatory variable to predict trace-element concentrations in bed sediment.

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

PubMed Central

Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

2015-01-01

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations. PMID:25234328

Administration of high doses of copper to capuchin monkeys does not cause liver damage but induces transcriptional activation of hepatic proliferative responses.

PubMed

Araya, Magdalena; Núñez, Héctor; Pavez, Leonardo; Arredondo, Miguel; Méndez, Marco; Cisternas, Felipe; Pizarro, Fernando; Sierralta, Walter; Uauy, Ricardo; González, Mauricio

2012-02-01

Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content, there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg⁻¹ . d⁻¹) and adult (7.5 mg Cu · kg⁻¹ . d⁻¹) capuchin monkeys would induce detectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3-3.5 y old at enrollment treated with copper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); young monkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2 males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liver histological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFβ, and NFκΒ only in adult monkeys. After 36 mo, the liver copper concentration was 4-5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage. Relative mRNA abundance of HGF, TGFβ and NFκB was significantly greater in ACu than in AC monkeys. In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expression of genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liver damage.

The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit

PubMed Central

Alissa, Eman M; Bahijri, Suhad M; Lamb, David J; Ferns, Gordon A A

2004-01-01

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25–1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination. PMID:15379959

Newly identified interfibrillar collagen crosslinking suppresses cell proliferation and remodelling.

PubMed

Marelli, Benedetto; Le Nihouannen, Damien; Hacking, S Adam; Tran, Simon; Li, Jingjing; Murshed, Monzur; Doillon, Charles J; Ghezzi, Chiara E; Zhang, Yu Ling; Nazhat, Showan N; Barralet, Jake E

2015-06-01

Copper is becoming recognised as a key cation in a variety of biological processes. Copper chelation has been studied as a potential anti-angiogenic strategy for arresting tumour growth. Conversely the delivery of copper ions and complexes in vivo can elicit a pro-angiogenic effect. Previously we unexpectedly found that copper-stimulated intraperitoneal angiogenesis was accompanied by collagen deposition. Here, in hard tissue, not only was healing accelerated by copper, but again enhanced deposition of collagen was detected at 2 weeks. Experiments with reconstituted collagen showed that addition of copper ions post-fibrillogenesis rendered plastically-compressed gels resistant to collagenases, enhanced their mechanical properties and increased the denaturation temperature of the protein. Unexpectedly, this apparently interfibrillar crosslinking was not affected by addition of glucose or ascorbic acid, which are required for crosslinking by advanced glycation end products (AGEs). Fibroblasts cultured on copper-crosslinked gels did not proliferate, whereas those cultured with an equivalent quantity of copper on either tissue culture plastic or collagen showed no effect compared with controls. Although non-proliferative, fibroblasts grown on copper-cross-linked collagen could migrate, remained metabolically active for at least 14 days and displayed a 6-fold increase in Mmps 1 and 3 mRNA expression compared with copper-free controls. The ability of copper ions to crosslink collagen fibrils during densification and independently of AGEs or Fenton type reactions is previously unreported. The effect on MMP susceptibility of collagen and the dramatic change in cell behaviour on this crosslinked ECM may contribute to shedding some light on unexplained phenomena as the apparent benefit of copper complexation in fibrotic disorders or the enhanced collagen deposition in response to localised copper delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Airborne copper exposure in school environments associated with poorer motor performance and altered basal ganglia.

PubMed

Pujol, Jesus; Fenoll, Raquel; Macià, Dídac; Martínez-Vilavella, Gerard; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Deus, Joan; Blanco-Hinojo, Laura; Querol, Xavier; Sunyer, Jordi

2016-06-01

Children are more vulnerable to the effects of environmental elements. A variety of air pollutants are among the identified factors causing neural damage at toxic concentrations. It is not obvious, however, to what extent the tolerated high levels of air pollutants are able to alter brain development. We have specifically investigated the neurotoxic effects of airborne copper exposure in school environments. Speed and consistency of motor response were assessed in 2836 children aged from 8 to 12 years. Anatomical MRI, diffusion tensor imaging, and functional MRI were used to directly test the brain repercussions in a subgroup of 263 children. Higher copper exposure was associated with poorer motor performance and altered structure of the basal ganglia. Specifically, the architecture of the caudate nucleus region was less complete in terms of both tissue composition and neural track water diffusion. Functional MRI consistently showed a reciprocal connectivity reduction between the caudate nucleus and the frontal cortex. The results establish an association between environmental copper exposure in children and alterations of basal ganglia structure and function.

Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species.

PubMed

Hadi, S M; Ullah, M F; Shamim, U; Bhatt, S H; Azmi, A S

2010-01-01

Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions. Copyright © 2010 S. Karger AG, Basel.

Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson’s Disease

PubMed Central

2016-01-01

Copper is an essential nutrient for life, but at the same time, hyperaccumulation of this redox-active metal in biological fluids and tissues is a hallmark of pathologies such as Wilson’s and Menkes diseases, various neurodegenerative diseases, and toxic environmental exposure. Diseases characterized by copper hyperaccumulation are currently challenging to identify due to costly diagnostic tools that involve extensive technical workup. Motivated to create simple yet highly selective and sensitive diagnostic tools, we have initiated a program to develop new materials that can enable monitoring of copper levels in biological fluid samples without complex and expensive instrumentation. Herein, we report the design, synthesis, and properties of PAF-1-SMe, a robust three-dimensional porous aromatic framework (PAF) densely functionalized with thioether groups for selective capture and concentration of copper from biofluids as well as aqueous samples. PAF-1-SMe exhibits a high selectivity for copper over other biologically relevant metals, with a saturation capacity reaching over 600 mg/g. Moreover, the combination of PAF-1-SMe as a material for capture and concentration of copper from biological samples with 8-hydroxyquinoline as a colorimetric indicator affords a method for identifying aberrant elevations of copper in urine samples from mice with Wilson’s disease and also tracing exogenously added copper in serum. This divide-and-conquer sensing strategy, where functional and robust porous materials serve as molecular recognition elements that can be used to capture and concentrate analytes in conjunction with molecular indicators for signal readouts, establishes a valuable starting point for the use of porous polymeric materials in noninvasive diagnostic applications. PMID:27285482

Antibacterial activity of agricultural waste derived wollastonite doped with copper for bone tissue engineering.

PubMed

Azeena, S; Subhapradha, N; Selvamurugan, N; Narayan, S; Srinivasan, N; Murugesan, R; Chung, T W; Moorthi, A

2017-02-01

Bioactive ceramic materials with metal ions generation brought great attention in the class of biomaterials development and widely employed as a filler material for bone tissue regeneration. The present study aimed to fabricate calcium silicate based ceramic material doped with copper metal particles by sol-gel method. Rice straw of agricultural waste was utilized as a source material to synthesize wollastonite, then wollastonite was doped with copper to fabricate copper doped wollastonite (Cu-Ws) particles. The synthesized materials were subjected to physio-chemical characterization by TEM, DLS, FTIR, XRD and DSC analysis. It was found that the sizes of the WS particles was around 900nm, while adding copper the size was increased upto 1184nm and the addition of copper to the material sharpening the peak. The release of Cu ions was estimated by ICP analysis. The anti-bacterial potentiality of the particles suggested that better microbial growth inhibition against E. coli (Gram negative) and S. aureus (Gram positive) strains from ATCC, in which the growth inhibition was more significant against S. aureus. The biocompatibility in mouse Mesenchymal Stem cells (mMSC) showed the non-toxic effect up to 0.05mg/ml concentration while the increase in concentration was found to be toxic to the cells. So the particles may have better potential application with the challenging prevention of post implantation infection in the field of bone tissue engineering (BTE). Copyright © 2016. Published by Elsevier B.V.

Marine Ecological Risk Assessment Pilot Study for Allen Harbor, Narragansett Bay, Rhode Island

DTIC Science & Technology

1992-01-01

evidence of major contamination in sediments or tissues except for relatively high levels of polychlorinated biphenols (PBC), butyltins compounds ( TBT ...biphenols (PBC), butyltin compounds ( TBT ), and fecal coliforms observed in Allen Harbor. Effects were detected in mussel physiology, sea urchin fertilization...Dichiorodiphenyl- dichioroethene HBC - Hexachlorobenzene TBT -Thbutyltin METALS Cu - Copper Zn -Zinc Cr - Chromium Pb -Lead Ni - Nickel As - Arsenic

Iron promotes protein insolubility and aging in C. elegans.

PubMed

Klang, Ida M; Schilling, Birgit; Sorensen, Dylan J; Sahu, Alexandria K; Kapahi, Pankaj; Andersen, Julie K; Swoboda, Peter; Killilea, David W; Gibson, Bradford W; Lithgow, Gordon J

2014-11-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity ofCaenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation.

Copper toxicity in Chinese cabbage is not influenced by plant sulphur status, but affects sulphur metabolism-related gene expression and the suggested regulatory metabolites.

PubMed

Shahbaz, M; Stuiver, C E E; Posthumus, F S; Parmar, S; Hawkesford, M J; De Kok, L J

2014-01-01

The toxicity of high copper (Cu) concentrations in the root environment of Chinese cabbage (Brassica pekinensis) was little influenced by the sulphur nutritional status of the plant. However, Cu toxicity removed the correlation between sulphur metabolism-related gene expression and the suggested regulatory metabolites. At high tissue Cu levels, there was no relation between sulphur metabolite levels viz. total sulphur, sulphate and water-soluble non-protein thiols, and the expression and activity of sulphate transporters and expression of APS reductase under sulphate-sufficient or-deprived conditions, in the presence or absence of H2 S. This indicated that the regulatory signal transduction pathway of sulphate transporters was overruled or by-passed upon exposure to elevated Cu concentrations. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Metabolic crossroads of iron and copper

PubMed Central

Collins, James F; Prohaska, Joseph R; Knutson, Mitchell D

2013-01-01

Interactions between the essential dietary metals, iron and copper, have been known for many years. This review highlights recent advances in iron-copper interactions with a focus on tissues and cell types important for regulating whole-body iron and copper homeostasis. Cells that mediate dietary assimilation (enterocytes) and storage and distribution (hepatocytes) of iron and copper are considered, along with the principal users (erythroid cells) and recyclers of red cell iron (reticuloendothelial macrophages). Interactions between iron and copper in the brain are also discussed. Many unanswered questions regarding the role of these metals and their interactions in health and disease emerge from this synopsis, highlighting extensive future research opportunities. PMID:20384844

Within- and among-population level differences in response to chronic copper exposure in southern toads, Anaxyrus terrestris.

PubMed

Lance, Stacey L; Flynn, R Wesley; Erickson, Matthew R; Scott, David E

2013-06-01

Environmental contaminants are implicated in the global decline of amphibian populations. Copper (Cu) is a widespread contaminant that can be toxic at concentrations just above the normal physiological range. In the present study we examined the effects of chronic Cu aqueous exposure on embryos and larvae of southern toads, Anaxyrus (Bufo) terrestris. Measurable levels of Cu were found in larvae, with tissue concentrations up to 27.5 μg Cu/g dry mass. Aqueous concentrations of Cu as low as 10 μg/L significantly reduced survival to the free-swimming stage and no larvae reached metamorphosis at concentrations above 15 μg/L. Clutches from populations with prior Cu exposure had the lowest survivorship. Among several populations there was significant variation in survivorship at different levels of Cu. More data are needed to understand the underlying causes of within- and among-population resilience to anthropogenic stressors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

PubMed Central

Kodama, Hiroko; Fujisawa, Chie; Bhadhprasit, Wattanaporn

2012-01-01

Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson’s disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome. Wilson’s disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson’s disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson’s disease should be implemented in infants. Patients with Wilson’s disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson’s disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention. PMID:21838703

Select tissue mineral concentrations and chronic wasting disease status in mule deer from North-central Colorado.

PubMed

Wolfe, Lisa L; Conner, Mary M; Bedwell, Cathy L; Lukacs, Paul M; Miller, Michael W

2010-07-01

Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (> or = 2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populations in north-central Colorado, United States, where CWD occurs naturally; we also measured copper concentrations in brain-stem (medulla oblongata at the obex) tissue from 181 of these deer. Analyses revealed a wide range of concentrations of all three minerals among sampled deer (copper: 5.6-331 ppm in liver, 1.5-31.9 ppm in obex; manganese: 0.1-21.4 ppm in liver; molybdenum: 0.5-4.0 ppm in liver). Bayesian multiple regression analysis revealed a negative association between obex copper (-0.097; 95% credible interval -0.192 to -0.006) and the probability of sampled deer also being infected with CWD, as well as a positive association between liver manganese (0.158; 95% credible interval 0.066 to 0.253) and probability of infection. We could not discern whether the tendencies toward lower brain-stem copper concentrations or higher systemic manganese concentrations in infected deer preceded prion infection or rather were the result of infection and its subsequent effects, although the distribution of trace mineral concentrations in infected deer seemed more suggestive of the latter.

IS COPPER REQUIRED FOR EASTERN OYSTER SETTING AND METAMORPHOSIS?

EPA Science Inventory

Recent field research with eastern oysters demonstrated higher defense activities, including hemocyte numbers, locomotion and bactericidal ability, associated with locations exhibiting relatively high contamination. Copper and zinc, found in high concentrations in tissues of oyst...

[Copper intake and blood levels as risk factors for atheromatous disease].

PubMed

Albala, C; Salazar, G; Vío, F; Araya, F; Feuerhacke, W; Olivares, S; Alvarez, G

1997-08-01

Copper is part of antioxidant enzymes and could have a cardiovascular protective effect. A higher cardiovascular risk has been associated with high as well as low plasma copper levels. To search for differences in copper intake and plasma levels between patients with coronary artery or cerebrovascular diseases and normal subjects. Zinc and copper intake, plasma levels and serum lipid levels were measured in 20 patients with cerebrovascular disease, 20 patients with an acute myocardial infarction and 40 subjects hospitalized for elective surgery, that served as controls. Copper and zinc intake was below recommended allowances in all subjects. Serum zinc and copper levels did not differ in the three study groups. In patients with myocardial infarction a weak correlation was found between serum copper and total cholesterol (r = 0.24; p < 0.05) and LDL cholesterol (r = 0.31; p < 0.05). No differences in copper levels were found in subjects with atherosclerosis and controls. The correlation between serum copper and cholesterol deserves further investigation.

Virgin olive oil blended polyurethane micro/nanofibers ornamented with copper oxide nanocrystals for biomedical applications.

PubMed

Amna, Touseef; Hassan, M Shamshi; Yang, Jieun; Khil, Myung-Seob; Song, Ki-Duk; Oh, Jae-Don; Hwang, Inho

2014-01-01

Recently, substantial interest has been generated in using electrospun biomimetic nanofibers of hybrids, particularly organic/inorganic, to engineer different tissues. The present work, for the first time, introduced a unique natural and synthetic hybrid micronanofiber wound dressing, composed of virgin olive oil/copper oxide nanocrystals and polyurethane (PU), developed via facile electrospinning. The as-spun organic/inorganic hybrid micronanofibers were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis, X-ray diffraction, electron probe microanalysis, and transmission electron microscopy. The interaction of cells with scaffold was studied by culturing NIH 3T3 fibroblasts on an as-spun hybrid micronanofibrous mat, and viability, proliferation, and growth were assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay results and SEM observation showed that the hybrid micronanofibrous scaffold was noncytotoxic to fibroblast cell culture and was found to benefit cell attachment and proliferation. Hence our results suggest the potential utilization of as-spun micronanoscaffolds for tissue engineering. Copper oxide-olive oil/PU wound dressing may exert its positive beneficial effects at every stage during wound-healing progression, and these micronanofibers may serve diverse biomedical applications, such as tissue regeneration, damaged skin treatment, wound healing applications, etc. Conclusively, the fabricated olive oil-copper oxide/PU micronanofibers combine the benefits of virgin olive oil and copper oxide, and therefore hold great promise for biomedical applications in the near future.

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria.

PubMed

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P; Yi, Ling; Kaler, Stephen G; Lutsenko, Svetlana; Ralle, Martina

2016-08-05

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria,more » whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).« less

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria*

PubMed Central

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

2016-01-01

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). PMID:27226607

Effects of metal mining and milling on boundary waters of Yellowstone National Park, USA

USGS Publications Warehouse

Nimmo, D.R.; Willox, M.J.; Lafrancois, T.D.; Chapman, P.L.; Brinkman, S.F.; Greene, J.C.

1998-01-01

Aquatic resources in Soda Butte Creek within Yellowstone National Park, USA, continue to be threatened by heavy metals from historical mining and milling activities that occurred upstream of the park's boundary. This includes the residue of gold, silver, and copper ore mining and processing in the early 1900s near Cooke City, Montana, just downstream of the creek's headwaters. Toxicity tests, using surrogate test species, and analyses of metals in water, sediments, and macroinvertebrate tissue were conducted from 1993 to 1995. Chronic toxicity to test species was greater in the spring than the fall and metal concentrations were elevated in the spring with copper exceeding water quality criteria in 1995. Tests with amphipods using pore water and whole sediment from the creek and copper concentrations in the tissue of macroinvertebrates and fish also suggest that copper is the metal of concern in the watershed. In order to understand current conditions in Soda Butte Creek, heavy metals, especially copper, must be considered important factors in the aquatic and riparian ecosystems within and along the creek extending into Yellowstone National Park.

The prooxidant action of dietary antioxidants leading to cellular DNA breakage and anticancer effects: implications for chemotherapeutic action against cancer.

PubMed

Ullah, M F; Ahmad, Aamir; Khan, Husain Y; Zubair, H; Sarkar, Fazlul H; Hadi, S M

2013-11-01

Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells.

Molecular evolution of the Slc15 family and its response to waterborne copper and mercury exposure in tilapia.

PubMed

Huang, Qiansheng; Vera Delgado, Juan Manuel; Seni Pinoargote, Oscar David; Llaguno, Ricardo Avellán

2015-06-01

The solute carrier 15 family (Slc15), also called oligopeptide transporter family (Pept), was well-known for its role in the cellular uptake of di/tripeptides and peptide-like molecules. Our understanding of Slc15 family has already been enlarged since the rapid increasing of genome information; however, efforts are still expected to reveal the diversification of the family in an evolutionary manner. In the study, the sequence information were collected and analyzed through eleven eukaryotic organism representatives, especially in fish species. Gene expansion was observed through the evolution of the family. Further study was carried out with the representative species-Nile tilapia (Oreochromis niloticus). Tissue expression profiles were compared among members of the Slc15 family. Generally, they were all highly expressed both in the intestine and stomach, however, different members possessed its special tissue expression pattern. The mRNA levels of all the members (except Slc15a4) decreased after fasting while refeeding could restore the expression level. The recovery ability was impaired after exposure to environmental relevant concentration of copper (Cu(2+), 160 nmol/L). By contrast, mercury (Hg(2+), 25 nmol/L) did not exert significant impact on the recovery ability. Copyright © 2015 Elsevier B.V. All rights reserved.

COPT6 is a plasma membrane transporter that functions in copper homeostasis in Arabidopsis and is a novel target of SQUAMOSA promoter binding protein-like 7

USDA-ARS?s Scientific Manuscript database

Among the mechanisms controlling copper homeostasis in plants is the regulation of its uptake and tissue partitioning. Here we characterized a newly identified member of the conserved CTR/COPT family of copper transporters in Arabidopsis thaliana, COPT6. We showed that COPT6 resides at the plasma me...

Cytokinin oxidase from Phaseolus vulgaris callus tissues. Enhanced in vitro activity of the enzyme in the presence of copper-imidazole complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatfield, J.M.; Armstrong, D.J.

1987-07-01

The effects of metal ions on cytokinin oxidase activity extracted from callus tissues of Phaseolus vulgaris L. cv Great Northern have been examined using an assay based on the oxidation of N/sup 6/-(..delta../sup 2/-isopentenyl)-adenine-2,8-/sup 3/H (i/sup 6/ Ade) to adenine (Ade). The addition of cupric ions to reaction mixtures containing imidazole buffer markedly enhanced cytokinin oxidase activity. In the presence of optimal concentrations of copper and imidazole, cytokinin oxidase activity was stimulated more than 20-fold. The effect was enzyme dependent, specific for copper, and observed only in the presence of imidazole. The substrate specificity of the copper-imidazole enhanced reaction, asmore » judged by substrate competition tests, was the same as that observed in the absence of copper and imidazole. Similarly, in tests involving DEAE-cellulose chromatography, elution profiles of cytokinin oxidase activity determined using a copper-imidazole enhanced assay were identical to those obtained using an assay without copper and imidazole. On the basis of these results, the addition of copper and imidazole to reaction mixtures used to assay for cytokinin oxidase activity is judged to provide a reliable and specific assay of greatly enhanced sensitivity for the enzyme. The mechanism by which copper and imidazole enhance cytokinin oxidase activity is not certain, but the reaction catalyzed by the enzyme was not inhibited by anaerobic conditions when these reagents were present. This observation suggests that copper-imidazole complexes are substituting for oxygen in the reaction mechanism by which cytokinin oxidase effects cleavage of the N/sup 6/-side chain of i/sup 6/ Ade.« less

Copper tolerance in clones of Agrostis gigantea from a mine waste site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, G.D.; Courtin, G.M.; Rauser, W.E.

1977-04-15

A mine waste site from Sudbury, Ontario, contaminated with heavy metals is described. The dominant vegetative cover was formed by two grasses: Agrostis gigantea Roth. and Agrostis scabra Willd. Testing of 10 clones of A. gigantea from the roast bed and an adjoining area for copper tolerance showed that two clones collected from the roast bed were tolerant to increased copper levels. Copper tolerance was found in clones growing on soils with high copper contents and low pHs. The combination of high copper content and low pH brought about a high level of extractable copper within the soil. Soils withmore » equally high copper levels but higher pHs and therefore low extractable-copper levels did not support copper-tolerant clones.« less

Biotransference and biomagnification of selenium copper, cadmium, zinc, arsenic and lead in a temperate seagrass ecosystem from Lake Macquarie Estuary, NSW, Australia.

PubMed

Barwick, M; Maher, W

2003-10-01

In this study the biotransference of selenium copper, cadmium, zinc, arsenic and lead was measured in a contaminated seagrass ecosystem in Lake Macquarie, NSW, Australia, to determine if biomagnification of these trace metals is occurring and if they reach concentrations that pose a threat to the resident organisms or human consumers. Selenium was found to biomagnify, exceeding maximum permitted concentrations for human consumption within carnivorous fish tissue, the highest trophic level examined. Selenium concentrations measured within carnivorous fish were also above those shown to elicit sub-lethal effects in freshwater fish. As comparisons are made to selenium concentrations known to effect freshwater fish, inferences must be made with caution. There was no evidence of copper, cadmium, zinc or lead biomagnification within the food web examined. Copper, cadmium, zinc and lead concentrations were below concentrations shown to elicit adverse responses in biota. Copper concentrations within crustaceans M. bennettae and P. palagicus were found to exceed maximum permitted concentrations for human consumption. It is likely that copper concentrations within these species were accumulated due to the essential nature of this trace metal for many species of molluscs and crustaceans. Arsenic showed some evidence of biomagnification. Total arsenic concentrations are similar to those found in other uncontaminated marine ecosystems, thus arsenic concentrations are unlikely to cause adverse effects to aquatic organisms. Inorganic arsenic concentrations are below maximum permitted concentrations for human consumption.

Serum copper levels in users of multiload intra-uterine contraceptive devices.

PubMed

Arowojolu, A O; Otolorin, E O; Ladipo, O A

1989-12-01

The systemic absorption of copper incorporated into multiload intra-uterine contraceptive devices (IUDs), as indicated by serum copper levels in users of such devices, was assessed in a prospective longitudinal study. One hundred and ten healthy Nigerian women using either multiload copper 250 (MLCU 250) or multiload copper 375 (MLCU 375) IUDs participated in the study. Their serum copper levels were estimated serially during 12 months of continuous use of the devices. The mean (+/- s.e.m.) pre-insertion serum copper levels of our subjects using MLCU 250 (17.0 +/- 3 mumol/l) and MLCU 375 (16.7 +/- 0.5 mumol/l) were found to be lower than those reported in Americans (22.2 mumol/l) and in Germans (20.2 mumol/l), although similar to levels in Indians (17.0 mumol/l). There was no significant difference in the mean serum copper levels estimated before and after 1 month of continuous use of the device. Serial estimations of the serum copper levels in users showed that there was no alteration in these levels after a period of 12 months of continuous IUD use. We therefore conclude that the copper incorporated into multiload IUDs appears not to influence the concentration of serum copper of users.

Bioavailable copper modulates oxidative phosphorylation and growth of tumors

PubMed Central

Ishida, Seiko; Andreux, Pénélope; Poitry-Yamate, Carole; Auwerx, Johan; Hanahan, Douglas

2013-01-01

Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment. PMID:24218578

Effects of contaminants on naiad mollusks (Unionidae): a review

USGS Publications Warehouse

Havlik, M.E.; Marking, L.L.

1987-01-01

Although the uptake, storage, and elimination of contaminants by naiad mollusks has been studied, relatively little information is available on toxicity. Contaminants appear to have destroyed some populations directly by exerting toxic effects, or indirectly by causing or contributing to the elimination of essential food organisms or host fish. The most frequently studied contaminants are Cd, Cu, Mn-Mn64, Pb-Pb210. and Zn-Zn65. Manganese seems to be most readily taken up and stored in tissues; no apparent damage has been reported from tissue concentrations of thousands of parts per million (ppm) and the element appears to be essential to metabolism. Zinc and cadmium also accumulate at high levels in tissues. Lead was never found to be lethal in the studies reviewed. Various common contaminants have been reported to be toxic at the following concentrations (ppm): cadmium. 2; copper sulfate, 2 to 18.7; ammonia, 5; potassium. 11; chromium, 12.4; arsenic trioxide, 16; copper, 19; and zinc, 66. In long-term exposures, concentrations of copper as low as 25 parts per billion (ppb) were lethal. Fry of fish infected with 20-35 glochidia were more sensitive than uninfected fish to toluene, naphthalene, and crude oil. Although few specific adverse impacts of contaminants have become clearly evident, circumstantial evidence leaves little doubt that contaminants have been responsible for decreases in population density, range, and diversity. Stresses that have been responsible for the disappearance of naiad mollusks in contaminated areas have not generally been identified, and the components of the stresses have seldom been quantitatively and qualitatively correlated with the composition and size of the naiad fauna. Often two or more factors appear to work in combination to produce the total stress that adversely affects populations. Naiad mollusks are important indio caters of contaminants in the environment; residues in soft tissue indicate recent or current exposure, and residues in shells indicate past exposure.

[Use of copper oxide wire particles (Copinox) for the prevention of congenital copper deficiency in a herd of German Improved Fawn breed of goat].

PubMed

Winter, P; Hochsteiner, W; Chizzola, R

2004-10-01

In a herd of German Improved Fawn breed of goat in the year 2000 neonatal kid losses due to congenital copper deficiencies were observed. To clarify the problems and to prevent losses in the next breeding season serum copper levels of 10 dams and four control Boer goats were investigated at four time points during one year. Additionally ten kids of the following year were sampled and the serum copper levels were studied. Immediatly after parturition and 8 weeks later the dams showed low serum copper levels (10.4 +/- 11.1 micromol/l, 5.7 +/- 2.9 micromol/l resp.). At the end of the pasture season an increase of serum copper could be measured (19.3 +/- 16.0 micromol/l). To prevent enzootic ataxia due to congenital copper deficiency, the dams were treated with copper oxide wire particles in the next late gestation. At this time point serum copper concentrations started to decrease (18.5 +/- 8.4 micromol/l). The re-examination 3 month later demonstrated an increase of the serum mean copper concentrations up to 23.4 micromol/l in the dams and to 16.2 micromol/l in the kids. The serum copper levels were significantly higher compared to the levels the year before. Big variation of the serum copper levels in the control Boer goats occurred during the year, but no clinical symptoms of copper deficiency could be observed. The copper levels in the grass and soil samples were 6.8 mg/kg and 0.2 mg/kg dry substance, respectively. A secondary copper deficiency based on cadmium could be excluded through the low levels of soil samples. The contents of sulphur and molybdenum were not determined. The results indicate that the German Improved Fawn breed of goats suffered from a primary copper deficiency due to the inefficient mineral supplementation. The administration of Copinox in the last third of the gestation leads to a continious raising of the copper concentrations in the serum and is suited to prevent ataxia due to congential copper deficiency in neonatal kids.

Copper deficiency in Tule Elk at Point Reyes, California

USGS Publications Warehouse

Gogan, Peter J.P.; Jessup, David A.; Akeson, Mark

1989-01-01

Tule elk (Cervus elaphus nannodes) reintroduced to Point Reyes, Calif., in 1978 exhibited gross signs of copper deficiency by June 1979. Copper levels in liver (x=5.9 ppm) and serum (0.42 ppm) of elk in Point Reyes were below levels in adult tule elk from other locations in California (liver, x=80 ppm; serum, x=1.4 ppm). These levels were consistent with documented copper deficiencies in wild and domestic ruminants. Copper serum levels increased in response to copper enriched dietary supplements and declined after the elk stopped eating the supplements. Analysis of plant and soil samples showed both are deficient in copper and normal in molybdenum and sulfur-sulfates. Deficiency in plants and soils at Point Reyes are probably due to low copper levels in the underlying granitic parent material.

The effects of the wood preservative copper dimethyldithiocarbamate in the hippocampus of maternal and newborn Long-Evans rats.

PubMed

Scharf, Brian; Trombetta, Louis David

2007-11-01

The potential toxic effects on human health and deleterious effects to the environment by copper dimethyldithiocarbamate (CDDC), an alternative wood preservative to chromated copper arsenate (CCA) have not been investigated. This study describes the neurotoxicity and accumulation of copper in the hippocampus of maternal and newborn Long-Evans rats following a subacute exposure to CDDC. Pregnant rats (220-270g) were treated daily with 0mg/kg, 25mg/kg, 50mg/kg, or 75mg/kg CDDC by oral gavage starting from day 6 of gestation and continuing to parturition. Following parturition, maternal and newborn rats were euthanized and brain tissues were removed, processed, and stored for analysis. Electron microscopy revealed demyelination and by-products of peroxidative damage in treated maternal hippocampi. Treated newborn hippocampi exhibited numerous degenerating mitochondria, membrane bound inclusion bodies, and vacuoles containing degraded structures. Graphite furnace atomic absorption spectrophotometry (GFAAS) demonstrated a significant increase in copper concentration in the tissues of treated animals as compared to controls. Western blot analysis revealed an induction of stress proteins HO-1 and Hsp70 and the formation of 4-hydroxy-2-nonenal (4HNE) adducts. CDDC was shown to be toxic to the brains, at all doses used and this toxicity is attributable to copper-induced lipid peroxidation.

Intestinal microbiota and lipid metabolism responses in the common carp (Cyprinus carpio L.) following copper exposure.

PubMed

Meng, Xiao-Lin; Li, Shuai; Qin, Chao-Bin; Zhu, Zhen-Xiang; Hu, Wen-Pan; Yang, Li-Ping; Lu, Rong-Hua; Li, Wen-Jun; Nie, Guo-Xing

2018-09-30

The present study was conducted to determine the effects of waterborne copper exposure on the lipid metabolism and intestinal microbiota of juvenile common carp (Cyprinus carpio L.). Common carp were exposed to four waterborne copper (Cu) concentrations (0 (control), 0.07 (low), 0.14 (medium), and 0.28 (high) mg Cu/L) for 8 weeks. Exposure to a high concentration of Cu had a negative effect on growth indices (weight gain rate (WGR) and specific growth rate (SGR)). The biochemical indices measured in serum (low-density lipoprotein (LDL) and triglycerides (TGs)) were significantly affected by exposure to medium concentration levels of Cu. The mRNA levels of lipogenic enzymes (acetyl-CoA carboxylase 1 (ACC-1) and fatty acid synthase (FAS)) and sterol-regulator element-binding protein-1 (SREBP-1) in liver tissue and tight binding protein genes (ZO-1 and occludin) in intestinal epithelial tissue were significantly downregulated in the 0.14 and 0.28 mg/L Cu treatment groups, accompanied by upregulated mRNA levels of lipolysis enzymes (lipoprotein lipase (LPL) and carnitine palmitoyl transferase 1 (CPT-1)) in the liver. The data also showed that the composition of intestinal microbiota was changed following Cu exposure and could alter the α-diversity and β-diversity. The abundances of few putative short-chain fatty acid (SCFA)-producing bacteria, including Allobaculum, Blautia, Coprococcus, Faecalibacterium, Roseburia, and Ruminococcus, decreased significantly. More specifically, Roseburia sequences were positively associated with lipogenic enzymes, total protein (TP), and TGs and negatively associated with lipolysis enzymes. Other sequences related to probiotics (Lactobacillus, Bacillus and Akkermansia) were also found to decrease, accompanied by an increase in sequences related to pathogens (Pseudomonas and Acinetobacter). To the best of our knowledge, the present study provides the first evidence that waterborne, chronic Cu exposure can disturb the composition of intestinal microbiota related to lipid metabolism and immunity in freshwater fish, thereby increasing the risk of pathogen invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

PubMed

Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

2017-09-15

Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Virgin olive oil blended polyurethane micro/nanofibers ornamented with copper oxide nanocrystals for biomedical applications

PubMed Central

Amna, Touseef; Hassan, M Shamshi; Yang, Jieun; Khil, Myung-Seob; Song, Ki-Duk; Oh, Jae-Don; Hwang, Inho

2014-01-01

Recently, substantial interest has been generated in using electrospun biomimetic nanofibers of hybrids, particularly organic/inorganic, to engineer different tissues. The present work, for the first time, introduced a unique natural and synthetic hybrid micronanofiber wound dressing, composed of virgin olive oil/copper oxide nanocrystals and polyurethane (PU), developed via facile electrospinning. The as-spun organic/inorganic hybrid micronanofibers were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis, X-ray diffraction, electron probe microanalysis, and transmission electron microscopy. The interaction of cells with scaffold was studied by culturing NIH 3T3 fibroblasts on an as-spun hybrid micronanofibrous mat, and viability, proliferation, and growth were assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay results and SEM observation showed that the hybrid micronanofibrous scaffold was noncytotoxic to fibroblast cell culture and was found to benefit cell attachment and proliferation. Hence our results suggest the potential utilization of as-spun micronanoscaffolds for tissue engineering. Copper oxide–olive oil/PU wound dressing may exert its positive beneficial effects at every stage during wound-healing progression, and these micronanofibers may serve diverse biomedical applications, such as tissue regeneration, damaged skin treatment, wound healing applications, etc. Conclusively, the fabricated olive oil–copper oxide/PU micronanofibers combine the benefits of virgin olive oil and copper oxide, and therefore hold great promise for biomedical applications in the near future. PMID:24611006

The effect of dietary zinc - and polyphenols intake on DMBA-induced mammary tumorigenesis in rats

PubMed Central

2012-01-01

Background The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements (Zn, Cu, Mg, Fe, Ca) in tumors as compared with normal tissue of the mammary gland. Methods Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA (7,12-dimethyl-1,2- benz[a]anthracene), were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES (inductively coupled plasma optical emission spectrometry) technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer. Results Regardless of the diet (standard; Zn; Zn + resveratrol; Zn + genistein), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found - irrespectively of the diet applied - great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue. Conclusions Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium content in the cancerous tissue in comparison with the healthy mammary tissue. The application of combined diet supplementation with zinc ions and resveratrol considerably promoted the rate of carcinogenesis and increased the number of DMBA-induced mammary tumors. PMID:22507225

Effect of Resveratrol Administration on the Element Metabolism in the Blood and Brain Tissues of Rats Subjected to Acute Swimming Exercise.

PubMed

Baltaci, Abdulkerim Kasim; Arslangil, Dilek; Mogulkoc, Rasim; Patlar, Suleyman

2017-02-01

The aim of the present study is to examine how resveratrol administration affects the element metabolism in the blood and brain cortex tissues of rats subjected to an acute swimming exercise. The study was carried out on Wistar-Albino-type adult male rats supplied by the Center. Group 1 is the control group. Group 2 is the swimming control group. Group 3 is the resveratrol (10 mg/kg/day) + swimming group. Group 4 is the resveratrol (10 mg/kg/day) group. Blood and brain cortex tissues were analyzed for some elements. The acute swimming exercise led to increases in the rats' serum iron, selenium, lead, cobalt, and boron levels, while the resveratrol-swimming group has increases in copper, phosphorus, and calcium values. The brain cortex tissue of the resveratrol-swimming group had significantly higher molybdenum levels than others. The results obtained in the study indicate that acute swimming exercise altered the distribution of elements in the serum to a considerable extent; however, resveratrol's affect is limited. Especially, resveratrol supplementation may have a regulatory affect on serum iron and magnesium levels.

A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.

PubMed

Yao, Mengyu; Ma, Lun; Li, Lihua; Zhang, Junying; Lim, Rebecca; Chen, Wei; Zhang, Yu

2016-10-01

Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

PubMed Central

Wachsmann, Jason; Peng, Fangyu

2016-01-01

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

[Determination of micro and macronutrients in the cattle of the Venezuelan plains and their influence on the origin of bovine paraplegic syndrome].

PubMed

Rojas, H; Serrano, J R; DiPolo, R

1994-01-01

We report a study carried out in three livestock-producing regions of Venezuela to determine the mineral status of grazing cattle and its relationship to the Síndrome Parpléjico del Bovino (SPB). Animal tissue samples from blood and liver were collected from a total of 17 farms within three regions: southwest (Apure), central (Guárico) and southeast (Bolívar) both during the dry and rainy seasons. In SPB free animals, the serum levels of sodium, potassium, chloride, magnesium, total and ionized calcium, phosphorus, and creatinine, were within the normal range. Glucose was found to be deficient in cattle from Bolívar and Guárico states and normal in Apure. With the exception of liver copper and serum zinc, all the other microelements analyzed (liver cobalt, and molybdenum, and serum iron) were found to be normal. Copper was found to be low in all regions studied with a mean value of 74.8 ppm indicating a moderate deficiency of this element. Similarly, in the central and southwest regions, zinc was found to be close to 0.34 ppm, significantly lower than the critical level of 0.7 ppm. In order to determine the effect of the dry and rainy seasons on the content of macro and microelements, controlled group of cattle from the three regions were followed in their contents of magnesium, calcium, copper and iron. In the dry season all of these elements tended to be much lower, showing a significant increase in the rainy season. This increase was much greater in cattle that received mineral supplementation and sanitary treatment. Bovines with diagnosis of SPB showed: low liver copper content, low serum magnesium and phosphorus levels significantly higher that control cattle.

[Measurement of the status of trace elements in cattle using liver biopsy samples].

PubMed

Ouweltjes, W; de Zeeuw, A C; Moen, A; Counotte, G H M

2007-02-01

Serum, plasma, or urine samples are usually used for the measurement of the trace elements copper; zinc, iron, selenium, because these samples are easy to obtain; however; these samples are not always appropriate. For example, it is not possible to measure molybdenum, the major antagonist of copper; in blood or urine. Therefore measurement of trace elements in liver tissue is considered the gold standard. For the assessment of selenium the method of choice remains determination of glutathion peroxidase in erythrocytes and for the assessment of magnesium determination of magnesium in urine. We determined the accuracy and repeatability of measuring trace elements in liver biopsies and whole liver homogenates. The levels of trace elements measured were similar in both preparations (92% agreement). Liver biopsy in live animals is a relatively simple procedure but not common in The Netherlands. Reference levels of trace elements, classified as too low, low, adequate, high, and too high, were established on the basis of our research and information in the literature. In a second study we investigated the practical aspects of obtaining liver tissue samples and their use. Samples were collected from cattle on a commercial dairy farm. Liver biopsy provided additional information to that obtained from serum and urine samples. We prepared a biopsy protocol and a test package, which we tested on 14 farms where an imbalance of trace minerals was suspected. Biopsy samples taken from 4 to 6 animals revealed extreme levels of trace elements.

The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients.

PubMed

Besiktepe, Neziha; Kayalar, Ozgecan; Ersen, Ezel; Oztay, Fusun

2017-12-01

Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n=35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1α), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1α immunoreactivity. Additionally, the emphysematous areas had significantly lower elastin, LOX, LOXL1, LOXL2, HIF-1α, COMMD1, and PTEN protein levels than the non-emphysematous areas. We suppose that the reductions in the HIF-1α levels led to decreases in the protein levels of active LOX, LOXL1, and LOXL2. These decreases might cause abnormalities in the elastic fiber biology. HIF-1α activation induced by decreased COMMD1 and protease activation induced by decreased PTEN might contribute to the development of PE. Finally, methods aimed at increasing the protein levels of LOXs, COMMD1 and PTEN might be effective for treating PE. Copyright © 2017 Elsevier GmbH. All rights reserved.

Effects of copper sulfate supplement on growth, tissue concentration, and ruminal solubilities of molybdenum and copper in sheep fed low and high molybdenum diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivan, M.; Veira, D.M.

1985-01-01

Each of four groups of six wethers were fed one of a low molybdenum, high molybdenum, high molybdenum plus copper sulfate, or high molybdenum plus copper sulfate corn silage-based diet for ad libitum intake for 221 days. Average daily gains and ratios of feed/gain were depressed for the high molybdenum diet as compared with the low molybdenum diet suggesting molybdenum toxicity in sheep fed the high molybdenum diet. This was alleviated partly by the copper sulfate supplement. The supplement also decreased solubility of both copper and molybdenum in the rumen but had no effect on copper concentration in blood plasma.more » Concentration of molybdenum was higher in both liver and kidney in sheep fed high-molybdenum diets as compared with low-molybdenum diets. Copper concentration was higher in kidneys of sheep fed high-molybdenum diets, but no difference was significant in liver copper between sheep fed diets high or low in molybdenum.« less

Laser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease

PubMed Central

Boaru, Sorina Georgiana; Merle, Uta; Uerlings, Ricarda; Zimmermann, Astrid; Flechtenmacher, Christa; Willheim, Claudia; Eder, Elisabeth; Ferenci, Peter; Stremmel, Wolfgang; Weiskirchen, Ralf

2015-01-01

Wilson's disease is an autosomal recessive disorder in which the liver does not properly release copper into bile, resulting in prominent copper accumulation in various tissues. Affected patients suffer from hepatic disorders and severe neurological defects. Experimental studies in mutant mice in which the copper-transporting ATPase gene (Atp7b) is disrupted revealed a drastic, time-dependent accumulation of hepatic copper that is accompanied by formation of regenerative nodes resembling cirrhosis. Therefore, these mice represent an excellent exploratory model for Wilson's disease. However, the precise time course in hepatic copper accumulation and its impact on other trace metals within the liver is yet poorly understood. We have recently established novel laser ablation inductively coupled plasma mass spectrometry protocols allowing quantitative metal imaging in human and murine liver tissue with high sensitivity, spatial resolution, specificity and quantification ability. By use of these techniques, we here aimed to comparatively analyse hepatic metal content in wild-type and Atp7b deficient mice during ageing. We demonstrate that the age-dependent accumulation of hepatic copper is strictly associated with a simultaneous increase in iron and zinc, while the intrahepatic concentration and distribution of other metals or metalloids is not affected. The same findings were obtained in well-defined human liver samples that were obtained from patients suffering from Wilson's disease. We conclude that in Wilson's disease the imbalances of hepatic copper during ageing are closely correlated with alterations in intrahepatic iron and zinc content. PMID:25704483

Iron promotes protein insolubility and aging in C. elegans

PubMed Central

Klang, Ida M.; Schilling, Birgit; Sorensen, Dylan J.; Sahu, Alexandria K.; Kapahi, Pankaj; Andersen, Julie K.; Swoboda, Peter; Killilea, David W.; Gibson, Bradford W.; Lithgow, Gordon J.

2014-01-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity of Caenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation. PMID:25554795

Fetal and neonatal iron deficiency but not copper deficiency increases vascular complexity in the developing rat brain

PubMed Central

Bastian, Thomas W.; Santarriaga, Stephanie; Nguyen, Thu An; Prohaska, Joseph R.; Georgieff, Michael K.; Anderson, Grant W.

2015-01-01

Objectives Anemia caused by nutritional deficiencies, such as iron and copper deficiencies, is a global health problem. Iron and copper deficiencies have their most profound effect on the developing fetus/infant, leading to brain development deficits and poor cognitive outcomes. Tissue iron depletion or chronic anemia can induce cellular hypoxic signaling. In mice, chronic hypoxia induces a compensatory increase in brain blood vessel outgrowth. We hypothesized that developmental anemia, due to iron or copper deficiencies, induces angiogenesis/vasculogenesis in the neonatal brain. Methods To test our hypothesis, three independent experiments were performed where pregnant rats were fed iron- or copper-deficient diets from gestational day 2 through mid-lactation. Effects on the neonatal brain vasculature were determined using qPCR to assess mRNA levels of angiogenesis/vasculogenesis-associated genes and GLUT1 immunohistochemistry (IHC) to assess brain blood vessel density and complexity. Results Iron deficiency, but not copper deficiency, increased mRNA expression of brain endothelial cell- and angiogenesis/vasculogenesis-associated genes (i.e. Glut1, Vwf, Vegfa, Ang2, Cxcl12, and Flk1) in the neonatal brain, suggesting increased cerebrovascular density. Iron deficiency also increased hippocampal and cerebral cortical blood vessel branching by 62% and 78%, respectively. Discussion This study demonstrates increased blood vessel complexity in the neonatal iron-deficient brain, which is likely due to elevated angiogenic/vasculogenic signaling. At least initially, this is probably an adaptive response to maintain metabolic substrate homeostasis in the developing iron-deficient brain. However, this may also contribute to long-term neurodevelopmental deficits. PMID:26177275

Influence of parasitism on trace element contents in tissues of red fox (Vulpes vulpes) and its parasites Mesocestoides spp. (Cestoda) and Toxascaris leonina (Nematoda).

PubMed

Jankovská, Ivana; Miholová, Daniela; Bejcek, Vladimír; Vadlejch, Jaroslav; Sulc, Miloslav; Száková, Jirina; Langrová, Iva

2010-02-01

Bioaccumulation of cadmium, chromium, copper, manganese, nickel, lead, and zinc in 56 foxes (Vulpes vulpes) and their parasites Mesocestoides spp. (Cestoda) and Toxascaris leonina (Nematoda) was studied. The levels of heavy metals were determined in the livers and kidneys of the animals depending on parasitism in the following ranges: Pb, 0.029-3.556; Cd, 0.055-9.967; Cr, 0.001-0.304; Cu, 4.15-41.15; Mn, 1.81-19.94; Ni: 0.037-0.831; Zn, 52.0-212.9 microg/g dry weight (dw). Cd in parasites (0.038-3.678 microg/g dw) were comparable with those in the livers of the host and lower than in the kidneys (0.095-6.032 microg/g dw). Contents of Pb, Cr, Cu, Mn, Ni, and Zn in cestodes were predominantly higher than those in the kidney and liver of the host. Median lead levels in Mesocestoides spp. (45.6 microg/g dw) were 52-fold higher than in the kidney and liver of the red fox (Vulpes vulpes) infected by both parasites and median Pb values in T. leonina (8.98 microg/g dw) were 8-fold higher than in the tissues of the parasitized red fox. Bioaccumulation factors of copper, zinc, nickel, and manganese are lower than those of lead and mostly range from 1.9 to 24 for Mesocestoides spp. and from 1.5 to 6 for nematode T. leonina depending on the tissue of host and element. A significant decrease in the content of Pb was found in the kidney of animals infected by T. leonina (0.260 microg/g dw) as well as those infected by Mesocestoides spp. (0.457 microg/g dw) in comparison with the lead content (0.878 microg/g dw) in the kidneys of the nonparasitized red fox. Regardless of a bioaccumulation of copper and manganese in the parasites, a significant increase of the concentrations of Mn and Cu was observed in the host's livers infected predominantly by Mesocestoides spp.

Estimating Dermal Transfer of Copper Particles from the ...

EPA Pesticide Factsheets

Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1 year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5 mg m-2) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1 month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was

Effectiveness of copper sulfate and potassium permanganate on channel catfish infected with Flavobacterium columnare

USDA-ARS?s Scientific Manuscript database

Copper sulfate (CuSO4) and potassium permanganate (KMnO4) were evaluated for their effectiveness to curtail mortality and decrease bacterial load in fish tissues and water in channel catfish Ictalurus punctatus naturally infected with Flavobacterium columnare, the causative agent of columnaris. Fis...

Investigating the influence of standard staining procedures on the copper distribution and concentration in Wilson's disease liver samples by laser ablation-inductively coupled plasma-mass spectrometry.

PubMed

Hachmöller, Oliver; Aichler, Michaela; Schwamborn, Kristina; Lutz, Lisa; Werner, Martin; Sperling, Michael; Walch, Axel; Karst, Uwe

2017-12-01

The influence of rhodanine and haematoxylin and eosin (HE) staining on the copper distribution and concentration in liver needle biopsy samples originating from patients with Wilson's disease (WD), a rare autosomal recessive inherited disorder of the copper metabolism, is investigated. In contemporary diagnostic of WD, rhodanine staining is used for histopathology, since rhodanine and copper are forming a red to orange-red complex, which can be recognized in the liver tissue using a microscope. In this paper, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method is applied for the analysis of eight different WD liver samples. Apart from a spatially resolved elemental detection as qualitative information, this LA-ICP-MS method offers also quantitative information by external calibration with matrix-matched gelatine standards. The sample set of this work included an unstained and a rhodanine stained section of each WD liver sample. While unstained sections of WD liver samples showed very distinct structures of the copper distribution with high copper concentrations, rhodanine stained sections revealed a blurred copper distribution with significant decreased concentrations in a range from 20 to more than 90%. This implies a copper removal from the liver tissue by complexation during the rhodanine staining. In contrast to this, a further HE stained sample of one WD liver sample did not show a significant decrease in the copper concentration and influence on the copper distribution in comparison to the unstained section. Therefore, HE staining can be combined with the analysis by means of LA-ICP-MS in two successive steps from one thin section of a biopsy specimen. This allows further information to be gained on the elemental distribution by LA-ICP-MS additional to results obtained by histological staining. Copyright © 2017 Elsevier GmbH. All rights reserved.

Computational study of the binding of CuII to Alzheimer's amyloid-beta peptide: do Abeta42 and Abeta40 bind copper in identical fashion?

PubMed

Mantri, Yogita; Fioroni, Marco; Baik, Mu-Hyun

2008-11-01

One of the many hypotheses on the pathogenesis of Alzheimer's disease is that the amyloid-beta peptide (Abeta) binds CuII and can catalytically generate H2O2, leading to oxidative damage in brain tissues. For a molecular level understanding of such catalysis it is critical to know the structure of the Abeta-CuII complex precisely. Unfortunately, no high-resolution structure is available to date and there is considerable debate over the copper coordination environment with no clear consensus on which residues are directly bound to CuII. Considering all plausible isomers of the copper-bound Abeta42 and Abeta40 using a combination of density functional theory and classical molecular dynamics methods, we report an atomic resolution structure for each possible complex. We evaluated the relative energies of these isomeric structures and surprisingly found that Abeta42 and Abeta40 display very different binding modes, suggesting that shorter peptides that are truncated at the C-terminus may not be realistic models for understanding the chemistry of the most neurotoxic peptide, Abeta42.

Classification of trace elements in tissues from organic and conventional French pig production.

PubMed

Parinet, Julien; Royer, Eric; Saint-Hilaire, Mailie; Chafey, Claude; Noël, Laurent; Minvielle, Brice; Dervilly-Pinel, Gaud; Engel, Erwan; Guérin, Thierry

2018-07-01

This study assesses the impact of the farming system on the levels of copper, zinc, arsenic, cadmium, lead and mercury in pig tissues from three types of production (Organic (n = 28), Label Rouge (n = 12) and Conventional (n = 30)) randomly sampled in different slaughterhouses. All the concentrations were below regulatory limits. In muscles, Cu, Zn and As were measured at slightly higher levels in organic samples but no differences between organic and Label Rouge was observed. Livers from conventional and Label Rouge pig farms exhibited higher Zn and Cd contents than the organic ones, probably due to different practice in zinc or phytase supplementation of fattening diets. Principal component analysis indicated a correlation between Cu and As concentrations in liver and carcass weight, and between Zn and Cd liver levels and lean meat percentage. The linear discriminant analysis succeeded in predicting the farming process on the basis of the lean meat percentage and the liver Cd level. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using Copper to Improve the Well-Being of the Skin

PubMed Central

Borkow, Gadi

2014-01-01

Copper has two key properties that are being exploited in consumer and medical device products in the last decade. On the one hand, copper has potent biocidal properties. On the other hand, copper is involved in numerous physiological and metabolic processes critical for the appropriate functioning of almost all tissues in the human body. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis. This manuscript reviews clinical studies that show that the use of textile consumer and medical device products, embedded with microscopic copper oxide particles, improve the well-being of the skin. These include studies showing a) cure of athlete’s foot infections and improvement in skin elasticity, especially important for individuals suffering from diabetes; b) reduction of facial fine line and wrinkles; and c) enhancement of wound healing; by copper oxide embedded socks, pillowcases and wound dressings, respectively. The manuscript also reviews and discusses the mechanisms by which the presence of copper in these products improves skin well-being. PMID:26361585

Genotoxic potential of copper oxide nanoparticles in the bivalve mollusk Mytilus trossulus

NASA Astrophysics Data System (ADS)

Chelomin, Victor P.; Slobodskova, Valentina V.; Zakhartsev, Maksim; Kukla, Sergey

2017-04-01

Copper oxide nanoparticles (CuO-NPs) are among the most widely used metal oxide nanoparticles, which increases the chance of their being released into the marine environment. As the applications of these particles have increased in recent years, their potential impact on the health of marine biota has also increased. However, the toxicological effects of these NPs in the marine environment are poorly known. In the present study, the DNA damaging potential of CuO-NPs in the marine eastern mussel Mytilus trossulus was evaluated and compared to that of dissolved copper exposures. Genotoxicity was assessed by the single cell gel electrophoresis (comet) assay in mussel gill and digestive gland cells. The results showed that copper in both forms (CuO-NPs and dissolved copper) was accumulated to different extents in mussel tissues. The mussel exposed to the dissolved copper attained higher concentrations of copper in the gills than in the digestive gland. In contrast to these results, it was found that CuO-NPs could induce much higher copper accumulation in the digestive gland than in the gills. A clear and statistically significant increase in DNA damage was found in both tissues of the Cu-exposed group compared to the control mussels. Our results indicated that the CuO-NP exposure produced remarkable effects and increased DNA damage significantly in mussel gill cells only. It should be noted that the digestive gland cells were prone to accumulation following CuO-NPs when compared to the gill cells, while the gill cells were more sensitive to the genotoxic effects of CuO-NPs. These results also suggested the need for a complete risk assessment of engineered particles before its arrival in the consumer market.

The Role of Grain Size on Neutron Irradiation Response of Nanocrystalline Copper

PubMed Central

Mohamed, Walid; Miller, Brandon; Porter, Douglas; Murty, Korukonda

2016-01-01

The role of grain size on the developed microstructure and mechanical properties of neutron irradiated nanocrystalline copper was investigated by comparing the radiation response of material to the conventional micrograined counterpart. Nanocrystalline (nc) and micrograined (MG) copper samples were subjected to a range of neutron exposure levels from 0.0034 to 2 dpa. At all damage levels, the response of MG-copper was governed by radiation hardening manifested by an increase in strength with accompanying ductility loss. Conversely, the response of nc-copper to neutron irradiation exhibited a dependence on the damage level. At low damage levels, grain growth was the primary response, with radiation hardening and embrittlement becoming the dominant responses with increasing damage levels. Annealing experiments revealed that grain growth in nc-copper is composed of both thermally-activated and irradiation-induced components. Tensile tests revealed minimal change in the source hardening component of the yield stress in MG-copper, while the source hardening component was found to decrease with increasing radiation exposure in nc-copper. PMID:28773270

Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering.

PubMed

Cattalini, Juan P; Roether, Judith; Hoppe, Alexander; Pishbin, Fatemeh; Haro Durand, Luis; Gorustovich, Alejandro; Boccaccini, Aldo R; Lucangioli, Silvia; Mouriño, Viviana

2016-10-21

Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate.

PubMed

Styczynski, Ashley R; Anwar, Khandaker N; Sultana, Habiba; Ghanem, Abdelhamid; Lurain, Nell; Chua, Aishi; Ghassemi, Mahmood; Novak, Richard M

2015-08-30

Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally. CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90. CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL. These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.

Chemical-specific health consultation for chromated copper arsenate chemical mixture: port of Djibouti.

PubMed

Chou, Selene; Colman, Joan; Tylenda, Carolyn; De Rosa, Christopher

2007-05-01

The Agency for Toxic Substances and Disease Registry (ATSDR) prepared this health consultation to provide support for assessing the public health implications of hazardous chemical exposure, primarily through drinking water, related to releases of chromated copper arsenate (CCA) in the port of Djibouti. CCA from a shipment, apparently intended for treating electric poles, is leaking into the soil in the port area. CCA is a pesticide used to protect wood against decay-causing organisms. This mixture commonly contains chromium(VI) (hexavalent chromium) as chromic acid, arsenic(V) (pentavalent arsenic) as arsenic pentoxide and copper (II) (divalent copper) as cupric oxide, often in an aqueous solution or concentrate. Experimental studies of the fate of CCA in soil and monitoring studies of wood-preserving sites where CCA was spilled on the soil indicate that the chromium(VI), arsenic and copper components of CCA can leach from soil into groundwater and surface water. In addition, at CCA wood-preserving sites, substantial concentrations of chromium(VI), arsenic and copper remained in the soil and were leachable into water four years after the use of CCA was discontinued, suggesting prolonged persistence in soil, with continued potential for leaching. The degree of leaching depended on soil composition and the extent of soil contamination with CCA. In general, leaching was highest for chromium(VI), intermediate for arsenic and lowest for copper. Thus, the potential for contamination of sources of drinking water exists. Although arsenic that is leached from CCA-contaminated soil into surface water may accumulate in the tissues of fish and shellfish, most of the arsenic in these animals will be in a form (often called fish arsenic) that is less harmful. Copper, which leaches less readily than the other components, can accumulate in tissues of mussels and oysters. Chromium is not likely to accumulate in the tissues of fish and shellfish. Limited studies of air concentrations during cleanup of CCA-contaminated soil at wood- preserving sites showed that air levels of chromium(VI), arsenic and copper were below the occupational standards. Workers directly involved in the repackaging, containment or cleanup of leaking containers of CCA or of soil saturated with CCA, however, may be exposed to high levels of CCA through direct dermal contact, inhalation of aerosols or particulates and inadvertent ingestion. Few studies have been conducted on the health effects of CCA. CCA as a concentrated solution is corrosive to the skin eyes and digestive tract. Studies of workers exposed to CCA in wood-preserving plants have not found adverse health effects in these workers, but the studies involved small numbers of workers and therefore are not definitive. People exposed to very high levels of CCA, from sawing wood that still had liquid CCA in it or from living in a home contaminated with ash containing high levels of chromium(VI), arsenic and copper, experienced serious health effects including nosebleeds, digestive system pain and bleeding, itching skin, darkened urine, nervous system effects such as tingling or numbness of the hands and feet and confusion, and rashes or thickening and peeling of the skin. These health effects of the mixture are at least qualitatively reflective of the health effects of the individual components of CCA (arsenic, chromium(VI) and copper). For a given mixture, the critical effects of the individual components are of particular concern, as are any effects in common that may become significant due to additivity or interactions among the components. Effects of concern for CCA, based on the known effects of the individual components, include cancer (arsenic by the oral route, arsenic and chromium(VI) by the inhalation route), irritant or corrosive effects (all three mixture components), the unique dermal effects of arsenic, neurologic effects (arsenic and chromium(VI), and hematologic, hepatic and renal effects (all three components). Because arsenic, chromium(VI), and copper components affect some of the same target organs, they may have additive toxicity toward those organs. Few studies have investigated the potential toxic interactions among the components (arsenic, chromium(VI) and copper) of CCA. The available interaction studies and also possible mechanisms of interaction were evaluated using a weight-of-evidence approach. The conclusion is that there is no strong evidence that interactions among the components of CCA will result in a marked increase in toxicity. This conclusion reflects a lack of well designed interaction studies as well as uncertainties regarding potential mechanisms of interaction. Confidence in the conclusion is low. Workers exposed to high levels of CCA during cleanup of leaking containers of CCA or soil heavily contaminated with CCA should wear protective clothing and respirators if air concentrations of arsenic are above 10 microg/m3. In addition, they should not eat, drink or use tobacco products during exposure to CCA, and should thoroughly wash after skin contact with CCA and before eating, drinking, using tobacco products or using restrooms. When protective clothing becomes contaminated with CCA, it should be changed, and the contaminated clothing should be disposed off in a manner approved for pesticide disposal. Workers should leave all protective clothing, including work shoes and boots, at the workplace, so that CCA will not be carried into their cars and homes, which would endanger other people. People not involved in the cleanup of the CCA and who are not wearing protective clothing should be prevented from entering contaminated areas. Leaking containers of CCA must be repackaged and contained to prevent direct exposure of on-site personnel; and contaminated soil needs to be removed to prevent the CCA from leaching into surface water and groundwater, thereby contaminating sources of drinking water.

THE IMPACT OF ORTHOPHOSPHATE ON COPPER CORROSION AND CHLORINE DEMAND

EPA Science Inventory

In 1991, EPA promulgated the Lead and Copper Rule, which established a copper action level of 1.3 mg/L in a 1-liter, first-draw sample collected from the consumer’s tap. Excessive corrosion of copper can lead to elevated copper levels at the consumer's tap, and in some cases, can...

Toxic effects of heavy metal Cu2+ on the pacific oyster Crassostrea gigas

NASA Astrophysics Data System (ADS)

Gao, Ceng; Zhang, Xinxin; Li, Xiumei; Tang, Xuexi

2017-05-01

The effects of different concentrations of heavy metal ions on the survival of the Pacific oyster Crassostrea gigas were studied by using experimental ecology method in 96 h. The results showed that the LC50 of copper ion was 21.748mg/L and the safe concentration was 2.1748mg/L mg/L. Under the condition of laboratory, under laboratory conditions, the research of Cu2+ Stress on the C. gigas gill and digestive gland and adductor muscle tissue SOD, GPx and the induction of CAT activity. The results showed that the activities of SOD, GPx and CAT in the C. gigas were significantly changed by copper ion + stress. The results showed that in the low concentration Cu2+ treatment could induce the three kinds of enzymes, in the high concentration Cu2+ treatment group, SOD and CAT and GPx on the inhibition of the effect. The sensitivity of the three antioxidant enzymes to copper ion showed a certain difference. The sensitivity of the three kinds of tissue enzymes to Cu2+ treatment was digestive gland> fascia> gill. The experimental results show that the single factor for copper in water pollutants, the C. gigas digestive gland tissue SOD, GPX and CAT activity has certain significance to it, but will it as index applied to the actual water need further study.

The effect of dietary copper supplementation on fatty acid profile and oxidative stability of adipose depots in Boer x Spanish goats.

PubMed

Cummins, K A; Solaiman, S G; Bergen, W G

2008-02-01

A feeding trial was designed to examine the effects of copper sulfate pentahydrate (CuSO(4).5H(2)O) on the fatty acid composition and oxidative stability in muscle and adipose tissues of Boer x Spanish goat kids. Fifteen (n = 5 per treatment) goats were fed 0, 100, or 200 mg of supplemental Cu per day as copper sulfate for 98 d. The animals were slaughtered, and LM, s.c. adipose from the sternal region, and mesenteric adipose tissues were collected. Total lipids were extracted with chloroform:methanol (2:1), methylated and isolated via GLC from all tissues. The subsequent peaks were then positively identified by mass spectrometry. Thiobarbituric acid-reactive substances were measured also. In s.c. adipose, dietary Cu significantly decreased C14:0 (P = 0.03) and C16:0 (P = 0.01). In muscle, C15:0 (P = 0.03) was linearly increased by Cu. Dietary Cu supplementation did not influence oxidative stability in goat muscle or s.c. adipose. Copper supplementation at 200 mg/d resulted in a significant increase in malondialdehyde in mesenteric adipose (P = 0.01) compared with the 0 or 100 mg/d groups. These results indicate that lipid composition may differ from depot to depot and that depending on the depot, dietary Cu seems to elicit a variable response on the fatty acid composition.

Elemental analysis of sunflower cataract in Wilson's disease: a study using scanning transmission electron microscopy and energy dispersive spectroscopy.

PubMed

Jang, Hyo Ju; Kim, Joon Mo; Choi, Chul Young

2014-04-01

Signature ophthalmic characteristics of Wilson's disease (WD) are regarded as diagnostically important manifestations of the disease. Previous studies have proved the common occurrence of copper accumulation in the liver of patients with WD. However, in the case of sunflower cataracts, one of the rare diagnostic signs of WD, no study has demonstrated copper accumulation in the lens capsules of sunflower cataracts in WD patients. To investigate the nanostructure and elemental composition of sunflower cataracts in WD, transmission electron microscopy (TEM) was done on the capsulorhexised anterior lens capsule of sunflower cataracts in WD in order to evaluate anatomical variation and elemental changes. We utilized energy dispersive X-ray spectroscopy (EDS) to investigate the elemental composition of the lens capsule using both point and mapping spectroscopy. Quantitative analysis was performed for relative comparison of the elements. TEM showed the presence of granular deposits of varying size (20-350 nm), appearing mainly in the posterior one third of the anterior capsule. The deposits appeared in linear patterns with scattered dots. There were no electron-dense particles in the epithelial cell layer of the lens. Copper and sulfur peaks were consistently revealed in electron-dense granular deposits. In contrast, copper and sulfur peaks were absent in other tissues, including granule-free lens capsules and epithelial tissue. Most copper was exclusively located in clusters of electron-dense particles, and the copper distribution overlapped with sulfur on mapping spectroscopy. Quantitative analysis presented inconsistent ratios of copper to sulfur in each electron-dense granule. The mean ratio of copper to sulfur was about 3.25 (with a range of 2.39-3.78). This is the first elemental analysis of single electron particles in sunflower cataracts using EDS in the ophthalmic area. Sunflower cataracts with WD are assumed to be the result of accumulation of heterogeneous compounds composed of several materials, including copper, sulfur, and/or copper-binding proteins. Linear patterns of copper and sulfur deposition were detected in various sizes and composition ratios with these elements in cases of WD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.

1989-01-01

We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles wasmore » confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload.« less

Influence of salicylic acid pretreatment on seeds germination and some defence mechanisms of Zea mays plants under copper stress.

PubMed

Moravcová, Šárka; Tůma, Jiří; Dučaiová, Zuzana Kovalíková; Waligórski, Piotr; Kula, Monika; Saja, Diana; Słomka, Aneta; Bąba, Wojciech; Libik-Konieczny, Marta

2018-01-01

The study was focused on the influence of salicylic acid (SA) on maize seeds germination and on some physiological and biochemical processes in maize plants growing in the hydroponic culture under copper (Cu) stress. A significant influence of SA pretreatment on the advanced induction of the maize seeds metabolic activity and the level of the endogenous SA in germinated seeds and developing roots have been stated. Although, the ability of maize seeds to uptake SA and accumulate it in the germinated roots was confirmed, the growth inhibition of Cu-stressed maize seedlings was not ameliorated by SA seeds pretreatment. Cu-stressed plants exhibited a decrease in the photosynthetic pigment concentration and the increase in non-photochemical quenching (NPQ) - an indicator of an excess energy in PSII antenna assemblies lost as a heat. The amelioration effect of SA application was found only for carotenoids content which increased in stressed plants. It was also shown that maize roots growing in stress conditions significantly differed in the chemical composition in comparison to the roots of control plants, but the SA pretreatment did not affect these differences. On the other hand, it was found that SA seed pretreatment significantly influenced the ability of stressed plants to accumulate copper in the roots. It was stated that a higher level of exogenous SA application led to a lower accumulation of Cu ions in maize roots. Cu-stressed plants exhibited higher oxidative stress in roots than in leaves which was manifested as an increase in the concentration of hydrogen peroxide due to stress factor application. We observed an increase in catalase (CAT) activity in leaves of Cu-stressed plants which corresponded with a lower H 2 O 2 content when compared with roots where the hydrogen peroxide level was higher, and the inhibition of the CAT activity was found. Furthermore, we found that the SA seed pretreatment led to a decrease in the H 2 O 2 content in the roots of the Cu-stressed plants, but it did not influence the H 2 O 2 level in leaves. The increase in hydrogen peroxide content in the roots of Cu-stressed plants correlated with a higher activity of the MnSODI and MnSODII isoforms. It was found that SA pretreatment caused a decrease in MnSODII activity accompanied by the decrease in H 2 O 2 concentration. Achieved results indicated also that the changes in the chemical composition of the root tissue under copper stress constituted protection mechanisms of blocking copper flow into other plant organs. However, it might be assumed that the root tissue remodelling under Cu stress did not only prevent against the Cu ions uptake but also limited the absorption of minerals required for the normal growth leading to the inhibition of the plant development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

PubMed

Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

2006-02-16

Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

A Family Knockout of All Four Drosophila Metallothioneins Reveals a Central Role in Copper Homeostasis and Detoxification†

PubMed Central

Egli, Dieter; Yepiskoposyan, Hasmik; Selvaraj, Anand; Balamurugan, Kuppusamy; Rajaram, Rama; Simons, Andreas; Multhaup, Gerd; Mettler, Simone; Vardanyan, Alla; Georgiev, Oleg; Schaffner, Walter

2006-01-01

Metallothioneins are ubiquitous, small, cysteine-rich proteins with the ability to bind heavy metals. In spite of their biochemical characterization, their in vivo function remains elusive. Here, we report the generation of a metallothionein gene family knockout in Drosophila melanogaster by targeted disruption of all four genes (MtnA to -D). These flies are viable if raised in standard laboratory food. During development, however, they are highly sensitive to copper, cadmium, and (to a lesser extent) zinc load. Metallothionein expression is particularly important for male viability; while copper load during development affects males and females equally, adult males lacking metallothioneins display a severely reduced life span, possibly due to copper-mediated oxidative stress. Using various reporter gene constructs, we find that different metallothioneins are expressed with virtually the same tissue specificity in larvae, notably in the intestinal tract at sites of metal accumulation, including the midgut's “copper cells.” The same expression pattern is observed with a synthetic minipromoter consisting only of four tandem metal response elements. From these and other experiments, we conclude that tissue specificity of metallothionein expression is a consequence, rather than a cause, of metal distribution in the organism. The bright orange luminescence of copper accumulated in copper cells of the midgut is severely reduced in the metallothionein gene family knockout, as well as in mutants of metal-responsive transcription factor 1 (MTF-1), the main regulator of metallothionein expression. This indicates that an in vivo metallothionein-copper complex forms the basis of this luminescence. Strikingly, metallothionein mutants show an increased, MTF-1-dependent induction of metallothionein promoters in response to copper, cadmium, silver, zinc, and mercury. We conclude that free metal, but not metallothionein-bound metal, triggers the activation of MTF-1 and that metallothioneins regulate their own expression by a negative feedback loop. PMID:16508004

Mechanism of Silver Nanoparticles Action on Insect Pigmentation Reveals Intervention of Copper Homeostasis

PubMed Central

Armstrong, Najealicka; Ramamoorthy, Malaisamy; Lyon, Delina; Jones, Kimberly; Duttaroy, Atanu

2013-01-01

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities past that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, we attempted to monitor the effects of AgNPs at a nonlethal concentration on wild type Drosophila melanogaster by exposing them throughout their development. All adult flies raised in AgNP doped food showed that up to 50 mg/L concentration AgNP has no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised due to AgNP feeding. Determination of the amount of free ionic silver (Ag+) led us to claim that the observed biological effects have resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, are decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Consequently, we propose a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explains the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, we claim that Drosophila, an established genetic model system, can be well utilized for further understanding of the biological effects of nanoparticles. PMID:23308159

Biological Mechanism of Silver Nanoparticle Toxicity

NASA Astrophysics Data System (ADS)

Armstrong, Najealicka Nicole

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further characterizing the biological effects of nanoparticles.

Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle.

PubMed Central

Schuschke, D. A.; Reed, M. W.; Saari, J. T.; Olson, M. D.; Ackermann, D. M.; Miller, F. N.

1992-01-01

The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion. PMID:1280989

The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients.

PubMed

Rodo, M; Czonkowska, A; Pulawska, M; Swiderska, M; Tarnacka, B; Wehr, H

2000-09-01

The aim of this study was to estimate the level of lipids and of the main serum antioxidant, alpha-tocopherol (vitamin E), and to evaluate the susceptibility of low density lipoprotein (LDL) to oxidation in Wilson's disease patients. It was assumed that enhanced LDL peroxidation caused by high copper levels could contribute to the injury of liver and other tissues. The group investigated comprised 45 individuals with Wilson's disease treated with penicillamine or zinc salts and a control group of 36 healthy individuals. Lipids were determined by enzymatic methods, alpha-tocopherol by high performance liquid chromatography, the susceptibility of LDL to oxidation in vitro by absorption changes at 234 nm during 5 h and end-products of LDL lipid oxidation as thiobarbituric acid reacting substances. In Wilson's disease patients total cholesterol, LDL cholesterol and alpha-tocopherol levels were significantly lower compared with the control group. No difference in LDL oxidation in vitro between the patients and the controls was stated. enhanced susceptibility of isolated LDL for lipid peroxidation in vitro was not observed in Wilson's disease patients. One cannot exclude, however, that because of low alpha-tocopherol level lipid peroxidation in the tissues can play a role in the pathogenesis of tissue injury in this disease.

Histopathological and bacterial study of skin and gill of grass carp, Ceteopharyngodon idella, (Valenciennes 1844) exposed to copper sulfate and potassium permanganate.

PubMed

Jooyandeh, Fatemeh; Sadeghpour, Ali; Khara, Hossein; Pajand, Zabihollah

2016-09-01

The gill histology and bacterial load of skin of the grass carp juveniles were investigated in relation to various concentrations of copper sulfate and potassium permanganate. For this purpose, the sublethal doses were determined after a pre-test and then the experiment was done in five treatments (for copper sulfate: 1, 1.94, 3.71, 7.07 and 15 mg/l and for potassium permanganate: 0.25, 0.52, 1.91, 2.27 and 5 mg/l) with three replicates inside the glass aquaria. Also, one group without disinfecting product was considered as control for each experiment. The microbial and histopathological investigations were done after 96 h exposure. According to results, the lowest bacterial load (CFU/g) of skin was observed in 15 mg/l copper sulfate treatment and 0.25 mg/l potassium permanganate treatment (P < 0.05). Also, the histological investigation showed a range of histopathological alternations in gills tissue including lamellar necrosis, hyperplasia, lamellar adhesion, haemorrhage, clubbing of gill lamellae. The severity of these alternations increased with increasing of the doses of the copper sulfate and potassium permanganate. In this regard, the highest histological damages were observed in 15 mg/l copper sulfate and 5 mg/l potassium permanganate respectively. Our results showed that low dosage of potassium permanganate has best effect on reducing of bacterial load of skin with lowest adverse effects on gill tissue.

Hypoxia induces copper stable isotope fractionation in hepatocellular carcinoma, in a HIF-independent manner.

PubMed

Bondanese, Victor P; Lamboux, Aline; Simon, Melanie; Lafont, Jérôme E; Albalat, Emmanuelle; Pichat, Sylvain; Vanacker, Jean-Marc; Telouk, Philippe; Balter, Vincent; Oger, Philippe; Albarède, Francis

2016-11-09

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, with increasing incidence worldwide. The unrestrained proliferation of tumour cells leads to tumour hypoxia which in turn promotes cancer aggressiveness. While changes in the concentration of copper (Cu) have long been observed upon cancerization, we have recently reported that the isotopic composition of copper is also altered in several types of cancer. In particular, we showed that in hepatocellular carcinoma, tumour tissue contains heavier copper compared to the surrounding parenchyma. However, the reasons behind such isotopic signature remained elusive. Here we show that hypoxia causes heavy copper enrichment in several human cell lines. We also demonstrate that this effect of hypoxia is pH, HIF-1 and -2 independent. Our data identify a previously unrecognized cellular process associated with hypoxia, and suggests that in vivo tumour hypoxia determines copper isotope fractionation in HCC and other solid cancers.

Studies of copper trafficking in a mouse model of Alzheimer's disease by positron emission tomography: comparison of 64Cu acetate and 64CuGTSM.

PubMed

Andreozzi, Erica M; Torres, Julia Baguña; Sunassee, Kavitha; Dunn, Joel; Walker-Samuel, Simon; Szanda, Istvan; Blower, Philip J

2017-11-15

Alzheimer's disease can involve brain copper dyshomeostasis. We aimed to determine the effect of AD-like pathology on 64 Cu trafficking in mice, using positron emission tomography (PET imaging), during 24 hours after intravenous administration of ionic 64 Cu (Cu(ii) acetate) and 64 Cu-GTSM (GTSMH 2 = glyoxalbis(thiosemicarbazone)). Copper trafficking was evaluated in 6-8-month-old and 13-15 month-old TASTPM transgenic and wild-type mice, by imaging 0-30 min and 24-25 h after intravenous administration of 64 Cu tracer. Regional 64 Cu distribution in brains was compared by ex vivo autoradiography to that of amyloid-β plaque. 64 Cu-acetate showed uptake in, and excretion through, liver and kidneys. There was minimal uptake in other tissues by 30 minutes, and little further change after 24 h. Radioactivity within brain was focussed in and around the ventricles and was significantly greater in younger mice. 64 CuGTSM was taken up in all tissues by 30 min, remaining high in brain but clearing substantially from other tissues by 24 h. Distribution in brain was not localised to specific regions. TASTPM mice showed no major changes in global or regional 64 Cu brain uptake compared to wildtype after administration of 64 Cu acetate (unlike 64 Cu-GTSM) but efflux of 64 Cu from brain by 24 h was slightly greater in 6-8 month-old TASTPM mice than in wildtype controls. Changes in copper trafficking associated with Alzheimer's-like pathology after administration of ionic 64 Cu are minor compared to those observed after administration of 64 Cu-GTSM. PET imaging with 64 Cu could help understand changes in brain copper dynamics in AD and underpin new clinical diagnostic imaging methods.

The Yeast Copper Response Is Regulated by DNA Damage

PubMed Central

Dong, Kangzhen; Addinall, Stephen G.; Lydall, David

2013-01-01

Copper is an essential but potentially toxic redox-active metal, so the levels and distribution of this metal are carefully regulated to ensure that it binds to the correct proteins. Previous studies of copper-dependent transcription in the yeast Saccharomyces cerevisiae have focused on the response of genes to changes in the exogenous levels of copper. We now report that yeast copper genes are regulated in response to the DNA-damaging agents methyl methanesulfonate (MMS) and hydroxyurea by a mechanism(s) that requires the copper-responsive transcription factors Mac1 and AceI, copper superoxide dismutase (Sod1) activity, and the Rad53 checkpoint kinase. Furthermore, in copper-starved yeast, the response of the Rad53 pathway to MMS is compromised due to a loss of Sod1 activity, consistent with the model that yeast imports copper to ensure Sod1 activity and Rad53 signaling. Crucially, the Mac1 transcription factor undergoes changes in its redox state in response to changing levels of copper or MMS. This study has therefore identified a novel regulatory relationship between cellular redox, copper homeostasis, and the DNA damage response in yeast. PMID:23959798

Perspectives on the Role and Relevance of Copper in Cardiac Disease.

PubMed

Medeiros, Denis M

2017-03-01

Cardiac hypertrophy as a result of dietary copper deficiency has been studied for 40 plus years and is the subject of this review. While connective tissue anomalies occur, a hallmark pathology is cardiac hypertrophy, increased mitochondrial biogenesis, with disruptive cristae, vacuolization of mitochondria, and deposition of lipid droplets. Electrocardiogram abnormalities have been demonstrated along with biochemical changes especially as it relates to the copper-containing enzyme cytochrome c oxidase. The master controller of mitochondrial biogenesis, PGC1-α expression and protein, along with other proteins and transcriptional factors that play a role are upregulated. Nitric oxide, vascular endothelial growth factor, and cytochrome c oxidase all may enhance the upregulation of mitochondrial biogenesis. Marginal copper intakes reveal similar pathologies in the absence of cardiac hypertrophy. Reversibility of the copper-deficient rat heart with a copper-replete diet has resulted in mixed results, depending on both the animal model used and temporal relationships. New information has revealed that copper supplementation may rescue cardiac hypertrophy induced by pressure overload.

Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections

PubMed Central

Mackie, Joanna; Ballou, Elizabeth R.; Childers, Delma S.; MacCallum, Donna M.; Feldmann, Joerg; Brown, Alistair J. P.

2016-01-01

Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits—metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease. PMID:27362522

A cytosolic copper storage protein provides a second level of copper tolerance in Streptomyces lividans.

PubMed

Straw, Megan L; Chaplin, Amanda K; Hough, Michael A; Paps, Jordi; Bavro, Vassiliy N; Wilson, Michael T; Vijgenboom, Erik; Worrall, Jonathan A R

2018-01-24

Streptomyces lividans has a distinct dependence on the bioavailability of copper for its morphological development. A cytosolic copper resistance system is operative in S. lividans that serves to preclude deleterious copper levels. This system comprises of several CopZ-like copper chaperones and P 1 -type ATPases, predominantly under the transcriptional control of a metalloregulator from the copper sensitive operon repressor (CsoR) family. In the present study, we discover a new layer of cytosolic copper resistance in S. lividans that involves a protein belonging to the newly discovered family of copper storage proteins, which we have named Ccsp (cytosolic copper storage protein). From an evolutionary perspective, we find Ccsp homologues to be widespread in Bacteria and extend through into Archaea and Eukaryota. Under copper stress Ccsp is upregulated and consists of a homotetramer assembly capable of binding up to 80 cuprous ions (20 per protomer). X-ray crystallography reveals 18 cysteines, 3 histidines and 1 aspartate are involved in cuprous ion coordination. Loading of cuprous ions to Ccsp is a cooperative process with a Hill coefficient of 1.9 and a CopZ-like copper chaperone can transfer copper to Ccsp. A Δccsp mutant strain indicates that Ccsp is not required under initial copper stress in S. lividans, but as the CsoR/CopZ/ATPase efflux system becomes saturated, Ccsp facilitates a second level of copper tolerance.

Nano Copper Induces Apoptosis in PK-15 Cells via a Mitochondria-Mediated Pathway.

PubMed

Zhang, Hui; Chang, Zhenyu; Mehmood, Khalid; Abbas, Rao Zahid; Nabi, Fazul; Rehman, Mujeeb Ur; Wu, Xiaoxing; Tian, Xinxin; Yuan, Xiaodan; Li, Zhaoyang; Zhou, Donghai

2018-01-01

Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40-100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly (P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.

Limited yield of diagnoses of intrahepatic infectious causes of canine granulomatous hepatitis from archival liver tissue.

PubMed

Hutchins, Rae G; Breitschwerdt, Edward B; Cullen, John M; Bissett, Sally A; Gookin, Jody L

2012-09-01

Canine granulomatous hepatitis is an uncommon morphologic diagnosis that has been associated with a variety of diseases, including a number of systemic infectious etiologies. Formalin-fixed, paraffin-embedded (FFPE) tissues are typically the only source of liver tissue remaining for additional testing for the presence of infectious disease within granulomas. It is unclear if the more common infectious culprits of granulomatous hepatitis can be identified from such specimens. The aim of the current study was to retrospectively investigate archival FFPE liver tissue from dogs with granulomatous hepatitis for the presence of infectious agents. Semiquantitative analysis of copper accumulation in liver specimens was also performed. Medical records were examined for recorded evidence of systemic infectious disease diagnosis. Formalin-fixed, paraffin-embedded liver was prospectively evaluated for infectious agents via differential staining techniques (n = 13), eubacterial fluorescent in situ hybridization (n = 11), and Bartonella polymerase chain reaction assays (n = 15). An infectious cause of granulomatous hepatitis was not identified within liver tissue from any dog using these diagnostic methodologies. Six out of 25 (24%) dogs were diagnosed with concurrent systemic or localized bacterial infections at the time of presentation. Nine out of 17 (53%) dogs had excessive hepatic copper accumulation when evaluated by a semiquantitative histologic grading scheme or quantitative copper analysis. As definitive infectious causes of granulomatous hepatitis were not identified within archival liver biopsy samples, it was concluded that investigation of infectious etiologies within FFPE liver specimens using these diagnostic approaches may be of low yield.

Histopathological and bacterial study of Persian sturgeon fry, Acipenser persicus (Borodin, 1897) exposed to copper sulfate and potassium permanganate.

PubMed

Moshtaghi, Batol; Khara, Hossein; Pazhan, Zabiyollah; Shenavar, Alireza

2016-09-01

Persian sturgeon frys were exposed to different concentrations of copper sulfate and potassium permanganate in order to the evaluation of their impacts on bacterial load of skin, gill and surrounding water and also the histopathological alternations of gill tissue. For this purpose, the sublethal doses were determined after a pre-test and then the experiment was done in 4 (for copper sulfate: 0.07, 0.14, 026 and 0.5 mg/l) and 5 (for potassium permanganate: 0.07, 0.14, 026, 0.5 and 1 mg/l) treatments with three replicates inside the glass aquaria. Also, one group without disinfecting drug was considered as control for each experiment. The microbial and histopathological investigations were done after 96 h exposure. According to our results, a range of histopathological alternations were observed in gills tissue including mucus coagulation and secretion, hyperplasia, lamellar necrosis, hyperplasia, lamellar adhesion, haemorrhage, thickening of secondary lamellae, hypertrophy of supporter cartilage, clubbing of gill lamellae and sliming of primary lamellae. The severity of these alternations increased with increasing of the doses of the copper sulfate and potassium permanganate. The bacterial load (CFU/g) of gill, skin and surrounding water was lower in 0.07 mg/l copper sulfate treatment and 1 mg/l potassium permanganate treatment (P < 0.05) than in other treatments. In conclusion, our results showed that the certain doses of the copper sulfate and potassium permanganate have disinfecting effects on bacterial load of gill, skin and surrounding water, although this is along with some histopathological alternations. Also, it seems that the copper sulfate has higher disinfecting power than potassium permanganate.

The Impact of Hexametaphosphate, Orthophosphate, and Temperature on Copper Corrosion and Release

EPA Science Inventory

Excessive corrosion of copper plumbing can lead to elevated copper levels at consumer’s tap or pinhole leaks. Corrosion control solutions include pH adjustment or phosphate addition. Orthophosphate has been shown to reduce copper levels in some cases while the role of polyphosp...

Testing the use of juvenile Salmo trutta L. as biomonitors of heavy metal pollution in freshwater.

PubMed

Lamas, S; Fernández, J A; Aboal, J R; Carballeira, A

2007-02-01

Individual specimens of Salmo trutta were captured, from four sampling sites in Galician rivers (NW Spain) affected by different types of contamination: diffuse urban waste, run-off from an unrestored dump at a copper mine and waste from a fish farm. The ages of the captured trouts were established and only those belonging to the 1+ age class were selected for study. The liver and kidney were removed from each fish and analysed to determine the tissue concentrations of Cu, Fe and Zn. The results obtained showed that: (i) the use of 1+ individuals allowed differentiation of contamination scenarios on the basis of the tissue concentrations of metal; (ii) the use of 1+ individuals allowed standardization of the time of exposure, which was sufficiently long for differential uptake to have taken place; (iii) liver tissue provided the best results as, less effort was required than for processing kidney tissue, and significant differences between sampling sites were detected because the intrapopulational variability in metal levels was lower than for kidney, and (iv) the levels of elements detected were not affected by basal tissue concentrations or residual concentrations due to past contamination, which older trouts may have been exposed to. In addition, the use of 1+ trout may provide better results in annual environmental sampling surveys.

Zinc and copper status of women by physical activity and menstrual status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, A.; Deuster, P.A.; Kyle, S.B.

The zinc and copper status of 33 eumenorrheic (EU) and 12 amenorrheic (AM) female marathon runners and 19 EU and 8 AM nonrunners were determined from 3-day diet records and plasma and erythrocyte (RBC) levels. The study was conducted as a completely randomized 2 x 2 factorial. Mean daily zinc intakes of all groups fell below the recommended dietary allowances. Copper intakes of runners (EU = 1.3 mg; AM = 1.3 mg) were not significantly different. Menstrual status did not affect plasma zinc, RBC zinc or plasma copper levels. Physical activity however, affected RBC zinc and plasma copper levels. Bothmore » these parameters were significantly higher in runners. These findings suggest that exercise influences blood zinc and copper levels.« less

SU-D-209-02: Percent Depth Dose Curves for Fluoroscopic X-Ray Beam Qualities Incorporating Copper Filtration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wunderle, K; Wayne State University School of Medicine, Detroit, MI; Godley, A

Purpose: The purpose of this investigation was to quantify percent depth dose (PDD) curves for fluoroscopic x-ray beam qualities incorporating added copper filtration. Methods: A PTW (Freiburg, Germany) MP3 water tank was used with a Standard Imaging (Middleton, WI) Exradin Model 11 Spokas Chamber to measure PDD curves for 60, 80, 100 and 120 kVp x-ray beams with copper filtration ranging from 0.0–0.9 mm at 22cm and 42cm fields of view from 0 to 150 mm of water. A free-in-air monitor chamber was used to normalize the water tank data to fluctuations in output from the fluoroscope. The measurements weremore » acquired on a Siemens (Erlangen, Germany) Artis ZeeGo fluoroscope. The fluoroscope was inverted from the typical orientation providing an x-ray beam originating from above the water tank. The water tank was positioned so that the water level was located at 60cm from the focal spot; which also represents the focal spot to interventional reference plane distance for that fluoroscope. Results: PDDs for 60, 80, 100, and 120 kVp with 0 mm of copper filtration compared well to previously published data by Fetterly et al. [Med Phys, 28, 205 (2001)] for those beam qualities given differences in fluoroscopes, geometric orientation, type of ionization chamber, and the water tank used for data collection. PDDs for 60, 80, 100, and 120 kVp with copper filtration were obtained and are presented, which have not been previously investigated and published. Conclusion: The equipment and processes used to acquire the reported data were sound and compared well with previously published data for PDDs without copper filtration. PDD data for the fluoroscopic x-ray beams incorporating copper filtration can be used as reference data for estimating organ or soft tissue dose at depth involving similar beam qualities or for comparison with mathematical models.« less

Chemical Data for Rock, Sediment, Biological, Precipitate, and Water Samples from Abandoned Copper Mines in Prince William Sound, Alaska

USGS Publications Warehouse

Koski, Randolph A.; Munk, LeeAnn

2007-01-01

In the early 20th century, approximately 6 million metric tons of copper ore were mined from numerous deposits located along the shorelines of fjords and islands in Prince William Sound, Alaska. At the Beatson, Ellamar, and Threeman mine sites (fig. 1), rocks containing Fe, Cu, Zn, and Pb sulfide minerals are exposed to chemical weathering in abandoned mine workings and remnant waste piles that extend into the littoral zone. Field investigations in 2003 and 2005 as well as analytical data for rock, sediment, precipitate, water, and biological samples reveal that the oxidation of sulfides at these sites is resulting in the generation of acid mine drainage and the transport of metals into the marine environment (Koski and others, 2008; Stillings and others, 2008). At the Ellamar and Threeman sites, plumes of acidic and metal-enriched water are flowing through beach gravels into the shallow offshore environment. Interstitial water samples collected from beach sediment at Ellamar have low pH levels (to ~3) and high concentrations of metals including iron, copper, zinc, cobalt, lead, and mercury. The abundant precipitation of the iron sulfate mineral jarosite in the Ellamar gravels also signifies a low-pH environment. At the Beatson mine site (the largest copper mine in the region) seeps containing iron-rich microbial precipitates drain into the intertidal zone below mine dumps (Foster and others, 2008). A stream flowing down to the shoreline from underground mine workings at Beatson has near-neutral pH, but elevated levels of zinc, copper, and lead (Stillings and others, 2008). Offshore sediment samples at Beatson are enriched in these metals. Preliminary chemical data for tissue from marine mussels collected near the Ellamar, Threeman, and Beatson sites reveal elevated levels of copper, zinc, and lead compared to tissue in mussels from other locations in Prince William Sound (Koski and others, 2008). Three papers presenting results of this ongoing investigation of sulfide oxidation in Prince William Sound are in press. Koski and others (2008) provide an overview of rock alteration, surface water chemistry, and the distribution of metals at the Ellamar, Threeman, and Beatson mine sites. Based on a 60-day, stream-discharge experiment at Beatson in 2005, Stillings and others (2008) analyze changes in water chemistry during storm events and the flux of metals to the shoreline. Foster and others (2008) investigate the biomass and diversity of microbial communities present in surface waters (streams, seeps, pore waters) using fatty acid methyl ester (FAMES) data and principal component analysis. The publications cited above contain a subset of the total chemical data for rock, sediment, biological, precipitate, and water samples collected from the three mine sites in 2003 and 2005. The purpose of this report is the presentation of complete chemical data sets for all samples collected during the two field periods of fieldwork. Data for a small number of samples collected at two other mines (Schlosser and Fidalgo, fig. 1), visited in 2003, are also included in the tables.

Chemical Data for Rock, Sediment, Biological, Precipitate, and Water Samples from Abandoned Copper Mines in Prince William Sound, Alaska

USGS Publications Warehouse

Koski, Randolph A.; Munk, LeeAnn

2007-01-01

Introduction In the early 20th century, approximately 6 million metric tons of copper ore were mined from numerous deposits located along the shorelines of fjords and islands in Prince William Sound, Alaska. At the Beatson, Ellamar, and Threeman mine sites (fig. 1), rocks containing Fe, Cu, Zn, and Pb sulfide minerals are exposed to chemical weathering in abandoned mine workings and remnant waste piles that extend into the littoral zone. Field investigations in 2003 and 2005 as well as analytical data for rock, sediment, precipitate, water, and biological samples reveal that the oxidation of sulfides at these sites is resulting in the generation of acid mine drainage and the transport of metals into the marine environment (Koski and others, 2008; Stillings and others, 2008). At the Ellamar and Threeman sites, plumes of acidic and metal-enriched water are flowing through beach gravels into the shallow offshore environment. Interstitial water samples collected from beach sediment at Ellamar have low pH levels (to ~3) and high concentrations of metals including iron, copper, zinc, cobalt, lead, and mercury. The abundant precipitation of the iron sulfate mineral jarosite in the Ellamar gravels also signifies a low-pH environment. At the Beatson mine site (the largest copper mine in the region) seeps containing iron-rich microbial precipitates drain into the intertidal zone below mine dumps (Foster and others, 2008). A stream flowing down to the shoreline from underground mine workings at Beatson has near-neutral pH, but elevated levels of zinc, copper, and lead (Stillings and others, 2008). Offshore sediment samples at Beatson are enriched in these metals. Preliminary chemical data for tissue from marine mussels collected near the Ellamar, Threeman, and Beatson sites reveal elevated levels of copper, zinc, and lead compared to tissue in mussels from other locations in Prince William Sound (Koski and others, 2008). Three papers presenting results of this ongoing investigation of sulfide oxidation in Prince William Sound are in press. Koski and others (2008) provide an overview of rock alteration, surface water chemistry, and the distribution of metals at the Ellamar, Threeman, and Beatson mine sites. Based on a 60-day, stream-discharge experiment at Beatson in 2005, Stillings and others (2008) analyze changes in water chemistry during storm events and the flux of metals to the shoreline. Foster and others (2008) investigate the biomass and diversity of microbial communities present in surface waters (streams, seeps, pore waters) using fatty acid methyl ester (FAMES) data and principal component analysis. The publications cited above contain a subset of the total chemical data for rock, sediment, biological, precipitate, and water samples collected from the three mine sites in 2003 and 2005. The purpose of this report is the presentation of complete chemical data sets for all samples collected during the two field periods of fieldwork. Data for a small number of samples collected at two other mines (Schlosser and Fidalgo, fig. 1), visited in 2003, are also included in the tables.

Levels of chemical contaminants in nonoccupationally exposed U. S. residents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holleman, J.W.; Hammons, A.S.

1978-08-01

Data are presented on the levels of all chemical contaminants resulting from environmental pollution which have been found in human tissues including blood, urine, breast milk, and tissue samples obtained at autopsy. Most data results from specific surveys to determine health hazards. The roles of trace elements and recognition of the need to determine baseline levels of chemicals introduced into the environment are factors which have motivated surveys by individual investigators. Thus, most data on chemicals in human tissues record levels of pesticides (e.g., DDT and metabolites), levels of trace metals such as lead, cadmium, and mercury, or levels ofmore » nutritionally essential elements such as zinc, copper, manganese, and fluoride. Data available on iron and calcium are not presented as their presence in the environment is generally not considered hazardous. Data on several uncommon chemicals, such as indium and ytterbium, are included basically as items of interest and to further document their presence in healthy individuals. Baseline data were presented where available to provide perspective as to chemical levels which might be expected under conditions where exposure could be considered normal or not directly related to a pollutant source. Nearly 600 cited surveys or investigations, most of which were reported within the past decade, are listed. Ninety-four different chemical contaminants, primarily trace metals and organochlorine pesticides, are reported. It is estimated that over 75% of the data published during the past 30 years on chemical contaminants derived from environmental pollution and found in human tissue in the United States are represented in this report.« less

Draft Genome Sequences of Four Alteromonas macleodii Strains Isolated from Copper Coupons and Grown Long-Term at Elevated Copper Levels.

PubMed

Cusick, Kathleen D; Dale, Jason R; Little, Brenda J; Biffinger, Justin C

2016-11-23

Alteromonas macleodii is a marine bacterium involved in the early stages of biofouling on ship hulls treated with copper as an antifouling agent. We report here the draft genome sequences of an A. macleodii strain isolated from copper coupons and three laboratory mutants grown long-term at elevated copper levels. Copyright © 2016 Cusick et al.

A practical comparison of Copper Bromide Laser for the treatment of vascular lesions.

PubMed

Lee, SunWoo; Lee, TaeBum; Kim, HoYoun; Kim, JungSoo; Eun, HyeJun; Kim, RyunKyung

2013-01-01

The recent rapid growth in demand for aesthetic non-invasive laser treatments such as unwanted skin rejuvenation, removal of age-related vascular blemishes has led to a boom in the medical devices to treat these conditions. Among diverse laser for skin treatment, copper bromide laser is a very effective, safe, and well tolerated treatment for facial telangiectasia at various energy levels and the most important thing of the copper bromide laser device is that the stability of the energy. However there is no evidence about effective copper bromide laser's energy level for the treatment of vascular lesions. We compared energy stability and treatment performance between two energy levels in 2 W and 8 W which commonly use in laser treatment for the vascular lesions. 8 W copper bromide laser was more stable compared than 2 W copper bromide laser. Also, 8 W copper bromide laser was effectively superior to 2 W copper bromide laser in treatment of vascular legion. Consequently, 8 W copper bromide laser treatment for vascular lesion might be more suitable than 2 W copper bromide laser.

Evaluation of the use of Leptodactylus ocellatus (Anura: Leptodactylidae) frog tissues as bioindicator of metal contamination in Contas River, Northeastern Brazil.

PubMed

Correia, Lívia O; Siqueira Júnior, Sérgio; Carneiro, Paulo L S; Bezerra, Marcos A

2014-12-01

This paper presents a study on the viability of the use of tissues of the Leptodactylus ocellatus species (Anura Leptodactylidae) as a bioindicator of metal pollution. The study is based on the determination and correlation of the concentrations of manganese, chromium, zinc, nickel, copper and iron in sediments and tissues (skin, muscles and viscera) of the frog Leptodactylus ocellatus collected in the middle region of the Contas River in Bahia, Brazil. The highest levels of the metals studied were found in the viscera of this animal. In this tissue, a higher correlation of the concentration of these metals with those found in sediments was also observed. The concentrations of elements found in the skin and muscles of these amphibians have revealed no correlation with the sediment where they were collected. According to the results obtained, the viscera of the L. ocellatus species presents itself as a good bioindicator of contamination by the metals studied.

Evaluation of the use of Leptodactylus ocellatus (Anura: Leptodactylidae) frog tissues as bioindicator of metal contamination in Contas River, Northeastern Brazil.

PubMed

Correia, Lívia O; Siqueira Júnior, Sérgio; Carneiro, Paulo L S; Bezerra, Marcos A

2014-10-24

This paper presents a study on the viability of the use of tissues of the Leptodactylus ocellatus species (Anura Leptodactylidae) as a bioindicator of metal pollution. The study is based on the determination and correlation of the concentrations of manganese, chromium, zinc, nickel, copper and iron in sediments and tissues (skin, muscles and viscera) of the frog Leptodactylus ocellatus collected in the middle region of the Contas River in Bahia, Brazil. The highest levels of the metals studied were found in the viscera of this animal. In this tissue, a higher correlation of the concentration of these metals with those found in sediments was also observed. The concentrations of elements found in the skin and muscles of these amphibians have revealed no correlation with the sediment where they were collected. According to the results obtained, the viscera of the L. ocellatus species presents itself as a good bioindicator of contamination by the metals studied.

40 CFR 141.80 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and copper action levels measured in samples collected at consumers' taps. (c) Lead and copper action levels. (1) The lead action level is exceeded if the concentration of lead in more than 10 percent of tap... action level is exceeded if the concentration of copper in more than 10 percent of tap water samples...

[The use of individual protective devices for decreasing the microbial contamination of the inhaled air].

PubMed

Sedov, A V; Akin'shin, A V; Tregub, T I

1995-01-01

The work was aimed to justify application of gas masks and respirators with autonomous air source fo lower bacterial contamination of inhaled air. The studies also covered possible catch of bacteria by cotton and filters FPP-15-1.5, those composed of antimicrobial materials, containing furagin or copper ions. As the studies proved, for lower bacterial contaminations of inhaled air one can apply autonomous air source apparatus with filters made of Petrianov tissue, antimicrobial tissue (containing furagin or copper ions), as they reduce fungal content of the air. Such filters are self-disinfecting, but do not influence total contamination of the air.

Membrane Lipid Peroxidation in Copper Alloy-Mediated Contact Killing of Escherichia coli

PubMed Central

Hong, Robert; Kang, Tae Y.; Michels, Corinne A.

2012-01-01

Copper alloy surfaces are passive antimicrobial sanitizing agents that kill bacteria, fungi, and some viruses. Studies of the mechanism of contact killing in Escherichia coli implicate the membrane as the target, yet the specific component and underlying biochemistry remain unknown. This study explores the hypothesis that nonenzymatic peroxidation of membrane phospholipids is responsible for copper alloy-mediated surface killing. Lipid peroxidation was monitored with the thiobarbituric acid-reactive substances (TBARS) assay. Survival, TBARS levels, and DNA degradation were followed in cells exposed to copper alloy surfaces containing 60 to 99.90% copper or in medium containing CuSO4. In all cases, TBARS levels increased with copper exposure levels. Cells exposed to the highest copper content alloys, C11000 and C24000, exhibited novel characteristics. TBARS increased immediately at a very rapid rate but peaked at about 30 min. This peak was associated with the period of most rapid killing, loss in membrane integrity, and DNA degradation. DNA degradation is not the primary cause of copper-mediated surface killing. Cells exposed to the 60% copper alloy for 60 min had fully intact genomic DNA but no viable cells. In a fabR mutant strain with increased levels of unsaturated fatty acids, sensitivity to copper alloy surface-mediated killing increased, TBARS levels peaked earlier, and genomic DNA degradation occurred sooner than in the isogenic parental strain. Taken together, these results suggest that copper alloy surface-mediated killing of E. coli is triggered by nonenzymatic oxidative damage of membrane phospholipids that ultimately results in the loss of membrane integrity and cell death. PMID:22247141

The antifertility effectiveness of copper/low-density polyethylene nanocomposite and its influence on the endometrial environment in rats.

PubMed

Liu, He-Fang; Liu, Zi-Long; Xie, Chang-Sheng; Yu, Jing; Zhu, Chang-Hong

2007-02-01

The study was conducted to investigate the antifertility effectiveness of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) and its influence on the endometrial environment in rats. One hundred and seventy sexually mature female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated control group (SO group, n=10), bulk copper group (Cu group, n=40), LDPE group (n=40), and nano-Cu/LDPE groups I (n=40) and II (n=40). Twenty rats in each group except for the SO group were mated with male rats of proven fertility, from 30 days after insertion, and the antifertility rates (ATs) were observed at Day 11 of pregnancy. The concentrations of prostaglandin E(2) (PGE(2)) and tissue plasminogen activator (tPA) in the endometrium of the remaining rats in each group were measured by using ELISA at the 30th and 60th day after insertion, respectively. ATs in the Cu group and nano-Cu/LDPE groups I and II (100%) were significantly higher than those in the LDPE group (p<.05). Compared with those in the SO group, the concentrations of PGE(2) and tPA in all experimental groups except for PGE(2) levels in the LDPE group were significantly increased at Day 30 after insertion, and these parameters in the nano-Cu/LDPE groups were significantly lower than in the Cu group (p<.05). At Day 60 after insertion, tPA levels were still higher in the Cu and nano-Cu/LDPE groups, but there was no difference in PGE(2) levels in all groups except for the Cu group. Nano-Cu/LDPE exhibits satisfactory contraceptive efficacy with less influence on the endometrium PGE(2) and tPA levels.

Metal accumulation by an epigean and a hypogean freshwater amphipod: Considerations for water quality assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pienet, S.

1999-12-01

To evaluate their potential as biomonitors of surface and underground water quality, the accumulation of essential metals, zinc and copper, by two species of amphipod crustaceans, Gammarus fossarum (an epigean amphipod) and Niphargus rhenorhodanensis (a similar but blind and hypogean form) was investigated. These two species were exposed, under controlled laboratory conditions, to different metal concentrations for 12 days. Several concentrations of each of the two metals separately and one concentration of a mixture of both were tested. Percent mortality revealed that the hypogean species was more resistant than the epigean. During the 12 days of experiment, accumulation patterns differedmore » between species and between metals. G. fossarum, but not N. rhenorhodanensis, accumulated zinc at exposures of up to 12 days and concentrations as great as 1,000 {micro}g/L. Zinc levels in tissue of G. fossarum were greater than in those of N. rhenorhodanensis. Epigean and hypogean amphipods did not clearly accumulate copper in exposures as great at 65 {micro}g/L. Possible reasons for the differences in zinc and copper accumulation between the two species are discussed. Finally, the suitability of the two species as biomonitors for surface and underground water is discussed.« less

Putting copper into action: copper-impregnated products with potent biocidal activities.

PubMed

Borkow, Gadi; Gabbay, Jeffrey

2004-11-01

Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids, and human tissue. Today copper is used as a water purifier, algaecide, fungicide, nematocide, molluscicide, and antibacterial and antifouling agent. Copper also displays potent antiviral activity. We hypothesized that introducing copper into clothing, bedding, and other articles would provide them with biocidal properties. A durable platform technology has been developed that introduces copper into cotton fibers, latex, and other polymeric materials. This study demonstrates the broad-spectrum antimicrobial (antibacterial, antiviral, antifungal) and antimite activities of copper-impregnated fibers and polyester products. This technology enabled the production of antiviral gloves and filters (which deactivate HIV-1 and other viruses), antibacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci), antifungal socks (which alleviate symptoms of athlete's foot), and anti-dust mite mattress covers (which reduce mite-related allergies). These products did not have skin-sensitizing properties, as determined by guine pig maximization and rabbit skin irritation tests. Our study demonstrates the potential use of copper in new applications. These applications address medical issues of the greatest importance, such as viral transmissions; nosocomial, or healthcare-associated, infections; and the spread of antibiotic-resistant bacteria.

Numerical investigation of vessel heating using a copper vapor laser and a pulsed dye laser in treating vascular skin lesions

NASA Astrophysics Data System (ADS)

Pushkareva, A. E.; Ponomarev, I. V.; Isaev, A. A.; Klyuchareva, S. V.

2018-02-01

A computer simulation technique was employed to study the selective heating of a tissue vessel using emission from a pulsed copper vapor laser and a pulsed dye laser. The depth and size of vessels that could be selectively and safely removed were determined for the lasers under examination.

Copper supplementation amplifies the anti-tumor effect of curcumin in oral cancer cells.

PubMed

Lee, Hui-Mei; Patel, Vyomesh; Shyur, Lie-Fen; Lee, Wai-Leng

2016-11-15

Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment. Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy. We hypothesized that intracellular copper levels may affect the sensitivity of oral cancer cells to curcumin. We analysed the correlation between intracellular copper levels and response to curcumin treatment in a panel of OSCC cell lines derived from oral cancer patients. Exogenous copper was supplemented in curcumin insensitive cell lines to observe the effect of copper on curcumin-mediated inhibition of cell viability and migration, as well as induction of oxidative stress and apoptosis. Protein markers of cell migration and oxidative stress were also analysed using Western blotting. Concentrations of curcumin which inhibited 50% OSCC cell viability (IC 50 ) was reduced up to 5 times in the presence of 250 µM copper. Increased copper level in curcumin-treated OSCC cells was accompanied by the induction of intracellular ROS and increased level of Nrf2 which regulates oxidative stress responses in cells. Supplemental copper also inhibited migration of curcumin-treated cells with enhanced level of E-cadherin and decreased vimentin, indications of suppressed epithelial-mesenchymal transition. Early apoptosis was observed in combined treatment but not in treatment with curcumin or copper alone. Supplement of copper significantly enhanced the inhibitory effect of curcumin treatment on migration and viability of oral cancer cells. Together, these findings provide molecular insight into the role of copper in overcoming insensitivity of oral cancer cells to curcumin treatment, suggesting a new strategy for cancer therapy. Copyright © 2016 Elsevier GmbH. All rights reserved.

Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model.

PubMed

Prinz, Cornelia; Elhensheri, Mohamed; Rychly, Joachim; Neumann, Hans-Georg

2017-08-01

Current strategies in implant technology are directed to generate bioactive implants that are capable to activate the regenerative potential of the surrounding tissue. On the other hand, implant-related infections are a common problem in orthopaedic trauma patients. To meet both challenges, i.e. to generate a bone implant with regenerative and antimicrobial characteristics, we tested the use of copper coated nails for surgical fixation in a rabbit model. Copper acetate was galvanically deposited with a copper load of 1 µg/mm 2 onto a porous oxide layer of Ti6Al4V nails, which were used for the fixation of a tibia fracture, inoculated with bacteria. After implantation of the nail the concentration of copper ions did not increase in blood which indicates that copper released from the implant was locally restricted to the fracture site. After four weeks, analyses of the extracted implants revealed a distinct antimicrobial effect of copper, because copper completely prevented both a weak adhesion and firm attachment of biofilm-forming bacteria on the titanium implant. To evaluate fracture healing, radiographic examination demonstrated an increased callus index in animals with copper coated nails. This result indicates a stimulated bone formation by releasing copper ions. We conclude that the use of implants with a defined load of copper ions enables both prevention of bacterial infection and the stimulation of regenerative processes.

The Application of Orthophosphate to Reduce Elevated Copper Levels in a New Building with High DIC Water

EPA Science Inventory

Public water utilities in the United States are required to meet the 1991 Lead and Copper Rule action level of 1.3 mg/L for copper I drinking water. The effect of water chemistry on Cu(II) solubility has been studied, and drawing upon conclusions from this research , new copper ...

SOLVING COPPER CORROSION PROBLEMS WHILE MAINTAINING LEAD CONTROL IN A HIGH ALKALINITY WATER USING ORTHOPHOSPHATE

EPA Science Inventory

Lead and Copper Rule sampling in 1992 uncovered high copper levels in many homes in the Indian Hill Water Works, Ohio (IHWW) water system. The 90th percentile copper and lead levels were 1.63 mg/L and 0.012 mg/L, respectively. IHWW supplies water to several suburban communities t...

Formation of copper precipitates in silicon

NASA Astrophysics Data System (ADS)

Flink, Christoph; Feick, Henning; McHugo, Scott A.; Mohammed, Amna; Seifert, Winfried; Hieslmair, Henry; Heiser, Thomas; Istratov, Andrei A.; Weber, Eicke R.

1999-12-01

The formation of copper precipitates in silicon was studied after high-temperature intentional contamination of p- and n-type FZ and Cz-grown silicon and quench to room temperature. With the Transient Ion Drift (TID) technique on p-type silicon a critical Fermi level position at EC-0.2 eV was found. Only if the Fermi level position, which is determined by the concentrations of the acceptors and the copper donors, surpasses this critical value precipitation takes place. If the Fermi level is below this level the supersaturated interstitial copper diffuses out. An electrostatic precipitation model is introduced that correlates the observed precipitation behavior with the electrical activity of the copper precipitates as detected with Deep Level Transient Spectroscopy (DLTS) on n-type and with Minority Carrier Transient Spectroscopy (MCTS) on p-type silicon.

Cancer risk in relation to serum copper levels.

PubMed

Coates, R J; Weiss, N S; Daling, J R; Rettmer, R L; Warnick, G R

1989-08-01

A nested, matched case-control study was conducted to assess the relationship between serum levels of copper and the subsequent risk of cancer. One hundred thirty-three cases of cancer were identified during 1974-1984 among 5000 members of a northwest Washington State employee cohort from whom serum specimens had been previously obtained and stored. Two hundred forty-one controls were selected at random from the cohort and were matched to the cases on the basis of age, sex, race, and date of blood draw. Serum copper levels were measured by atomic absorption spectrometry. Risk of a subsequent diagnosis of cancer was positively associated with serum copper levels, but only among those cases diagnosed within 4 years of the time the serum specimens were collected. Among cases diagnosed more than 4 years after specimen collection, there was no consistent association between serum copper levels and risk. Adjustment for age, sex, race, occupational status, cigarette smoking, family history of cancer, alcohol consumption, and, among females, use of exogenous hormones had no appreciable effect on these relationships. The findings suggest that the presence of cancer may increase serum copper levels several years prior to its diagnosis. They are less supportive of the hypothesis that serum copper levels affect cancer risk.

Copper and the Prion Protein: Methods, Structures, Function, and Disease

NASA Astrophysics Data System (ADS)

Millhauser, Glenn L.

2007-05-01

The transmissible spongiform encephalopathies (TSEs) arise from conversion of the membrane-bound prion protein from PrPC to PrPSc. Examples of the TSEs include mad cow disease, chronic wasting disease in deer and elk, scrapie in goats and sheep, and kuru and Creutzfeldt-Jakob disease in humans. Although the precise function of PrPC in healthy tissues is not known, recent research demonstrates that it binds Cu(II) in an unusual and highly conserved region of the protein termed the octarepeat domain. This review describes recent connections between copper and PrPC, with an emphasis on the electron paramagnetic resonance elucidation of the specific copper-binding sites, insights into PrPC function, and emerging connections between copper and prion disease.

Ecophysiological and metabolic responses to interactive exposure to nutrients and copper excess in the brown macroalga Cystoseira tamariscifolia.

PubMed

Celis-Plá, Paula S M; Brown, Murray T; Santillán-Sarmiento, Alex; Korbee, Nathalie; Sáez, Claudio A; Figueroa, Félix L

2018-03-01

Global scenarios evidence that contamination due to anthropogenic activities occur at different spatial-temporal scales, being important stressors: eutrophication, due to increased nutrient inputs; and metal pollution, mostly derived from industrial activities. In this study, we investigated ecophysiological and metabolic responses to copper and nutrient excess in the brown macroalga Cystoseira tamariscifolia. Whole plants were incubated in an indoor system under control conditions, two levels of nominal copper (0.5 and 2.0μM), and two levels of nutrient supply for two weeks. Maximal quantum yield (F v /F m ) and maximal electron transport rate (ETR max ) increased under copper exposure. Photosynthetic pigments and phenolic compounds (PC) increased under the highest copper levels. The intra-cellular copper content increased under high copper exposure in both nutrient conditions. C. tamariscifolia from the Atlantic displayed efficient metal exclusion mechanisms, since most of the total copper accumulated by the cell was bound to the cell wall. Copyright © 2018 Elsevier Ltd. All rights reserved.

Relationship between 578-nm (copper vapor) laser beam geometry and heat distribution within biological tissues

NASA Astrophysics Data System (ADS)

Ilyasov, Ildar K.; Prikhodko, Constantin V.; Nevorotin, Alexey J.

1995-01-01

Monte Carlo (MC) simulation model and the thermoindicative tissue phantom were applied for evaluation of a depth of tissue necrosis (DTN) as a result of quasi-cw copper vapor laser (578 nm) irradiation. It has been shown that incident light focusing angle is essential for DTN. In particular, there was a significant rise in DTN parallel to elevation of this angle up to +20 degree(s)C and +5 degree(s)C for both the MC simulation and tissue phantom models, respectively, with no further increase in the necrosis depth above these angles. It is to be noted that the relationship between focusing angles and DTN values was apparently stronger for the real target compared to the MC-derived hypothetical one. To what extent these date are applicable for medical practice can be evaluated in animal models which would simulate laser-assisted therapy for PWS or related dermatologic lesions with converged 578 nm laser beams.

L-threo 3,4-dihydroxyphenylserine treatment during mouse perinatal and rat postnatal development does not alter the impact of dietary copper deficiency

PubMed Central

Pyatskowit, Joshua W.; Prohaska, Joseph R.

2009-01-01

Dietary copper (Cu) deficiency was induced perinatally in Swiss Albino mice and postnatally in male Holtzman rats to investigate the effect of L-threo 3,4-dihydroxyphenylserine (DOPS) on pup survival and catecholamine levels in a 2 × 2 factorial design. Mouse dams were placed on one of four treatments 14 days after mating and rats at postnatal day 19 (P19). Treatments were Cu-adequate (Cu +) and Cu-deficient (Cu −) diets with or without DOPS (1 mg/ml) in the drinking water. Mouse pups were killed at P14 and rats at P49. Mortality in Cu − pups was 46% and not significantly improved by DOPS, 39%. A repeat study with mice adding ascorbic acid in the water with DOPS showed no improvement. Compared to Cu + animals, Cu − animals were smaller, anemic and had a 92% reduction in liver Cu. DOPS treatment made no improvement to and in some cases exacerbated the Cu deficiency. Catecholamine levels measured in heart and brain by LCEC showed decreased NE levels and increased DA levels in Cu − animals compared to controls. DOPS treatment did not alter this pattern. Although DOPS was present in treated animal’s tissues, survival in mice and catecholamine levels in mice and rats were not altered by the 1 mg/ml dose of DOPS. PMID:16117185

The effect of red cell and plasma transfusion on serum zinc and copper levels in the neonate.

PubMed

Lockitch, G; Godolphin, W J; Pendray, M R; Quigley, G

1983-11-01

Transfusion of packed red cells (15 to 20 ml/kg) in 11 preterm infants resulted in a slight increase in mean serum zinc levels on the 3rd post transfusion day but no effect was noted on serum copper levels. No significant difference was found between the changes in serum zinc in 141 paired specimens collected a week apart when zero, one, two or three packed cell transfusions were given in the intervening week. A slight decrease in the mean copper level was noted when one transfusion was given. Transfusion of fresh frozen plasma in six newborns with abdominal wall defects resulted in initial serum copper levels two to three times greater than the reference mean for newborns. No effect was noted on zinc levels. Serum copper results should be interpreted with caution in infants who have been transfused with plasma.

Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

PubMed

Hu Frisk, Jun Mei; Kjellén, Lena; Kaler, Stephen G; Pejler, Gunnar; Öhrvik, Helena

2017-12-15

Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

Cadmium, copper, iron, and zinc concentrations in kidneys of grey wolves, Canis lupus, from Alaska, Idaho, Montana (USA) and the Northwest Territories (Canada).

PubMed

Hoffmann, S R; Blunck, S A; Petersen, K N; Jones, E M; Koval, J C; Misek, R; Frick, J A; Cluff, H D; Sime, C A; McNay, M; Beckman, K B; Atkinson, M W; Drew, M; Collinge, M D; Bangs, E E; Harper, R G

2010-11-01

Cadmium, copper, iron, and zinc levels were measured in the kidneys of 115 grey wolves (Canis lupus) from Idaho, Montana and Alaska (United States), and from the Northwest Territories (Canada). No significant differences in the levels of iron or copper were observed between locations, but wolf kidneys from more northern locations had significantly higher cadmium levels (Alaska > Northwest Territories > Montana ≈ Idaho), and wolves from Alaska showed significantly higher zinc than other locations. Additionally, female wolves in Alaska had higher iron levels than males, and adult wolves in Montana had higher copper levels than subadults.

The Determination of Trace Metals in Saline Waters and Biological Tissues Using the Heated Graphite Atomizer

NASA Technical Reports Server (NTRS)

Segar, D. A.

1971-01-01

A selective, volatalization technique utilizing the heated graphite atomizer atomic absorption technique has been developed for the analysis of iron in sea water. A similar technique may be used to determine vanadium, copper, nickel and cobalt in saline waters when their concentrations are higher than those normally encountered'in unpolluted sea waters. A preliminary solvent extraction using ammonium pyrolidine dithiocarbamate and methyl iso-butyl ketone permits the determination of a number of elements including iron, copper, zinc, nickel, cobalt and lead in sea water. The heated graphite atomized technique has also been applied to the determination of a range of trace transition elements in marine plant and animal tissues.

Estimation of copper in saliva and areca nut products and its correlation with histological grades of oral submucous fibrosis.

PubMed

Mohammed, Faraz; Manohar, Vidya; Jose, Maji; Thapasum, Arishiya Fairozekhan; Mohamed, Shamaz; Shamaz, Bibi Halima; D'Souza, Neevan

2015-03-01

The purpose of this study was to estimate the copper levels in saliva of patients with oral submucous fibrosis (OSF) and different areca nut products and its correlation with different histological grades of OSF. The study comprised 60 individuals, 30 OSF patients and 30 non-OSF individuals. Unstimulated whole saliva was collected, and copper analysis was performed using colorimetric method. The commercial areca nut products used by the patients were acquired and subjected to copper analysis through the atomic absorption spectrophotometer method. Oral biopsies were performed for OSF patients for histopathological correlation. The mean salivary copper level was 27.023 μg/dl in OSF patients when compared with 8.393 μg/dl in non-OSF individuals (P < 0.005). The mean copper content in different areca nut products was 13.313 ppm (P < 0.005). Comparison of copper content in different areca nut products with salivary copper levels of OSF patients showed negative correlation (P < 0.853). Comparison of salivary copper levels between different histological grades of OSF yielded a statistically significant association between grades I and III (P < 0.005) and grades II and III OSF (P < 0.019). Comparison of copper content in areca nut products and different histological grades of OSF yielded weak negative statistical correlation (r = -0.116). Despite high copper content in areca nut products, the observations yielded a negative correlation with different histological grades of OSF. This further raises a doubt about the copper content in areca nut as an etiological factor for this crippling disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular Mediators Governing Iron-Copper Interactions

PubMed Central

Gulec, Sukru; Collins, James F.

2015-01-01

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

Organochlorine compounds and trace elements in fish tissue and bed sediments in the lower Snake River basin, Idaho and Oregon

USGS Publications Warehouse

Clark, Gregory M.; Maret, Terry R.

1998-01-01

Fish-tissue and bed-sediment samples were collected to determine the occurrence and distribution of organochlorine compounds and trace elements in the lower Snake River Basin. Whole-body composite samples of suckers and carp from seven sites were analyzed for organochlorine compounds; liver samples were analyzed for trace elements. Fillets from selected sportfish were analyzed for organochlorine compounds and trace elements. Bed-sediment samples from three sites were analyzed for organochlorine compounds and trace elements. Twelve different organochlorine compounds were detected in 14 fish-tissue samples. All fish-tissue samples contained DDT or its metabolites. Concentrations of total DDT ranged from 11 micrograms per kilogram wet weight in fillets of yellow perch from C.J. Strike Reservoir to 3,633 micrograms per kilogram wet weight in a whole-body sample of carp from Brownlee Reservoir at Burnt River. Total DDT concentrations in whole-body samples of sucker and carp from the Snake River at C.J. Strike Reservoir, Snake River at Swan Falls, Snake River at Nyssa, and Brownlee Reservoir at Burnt River exceeded criteria established for the protection of fish-eating wildlife. Total PCB concentrations in a whole-body sample of carp from Brownlee Reservoir at Burnt River also exceeded fish-eating wildlife criteria. Concentrations of organochlorine compounds in whole-body samples, in general, were larger than concentrations in sportfish fillets. However, concentrations of dieldrin and total DDT in fillets of channel catfish from the Snake River at Nyssa and Brownlee Reservoir at Burnt River, and concentrations of total DDT in fillets of smallmouth bass and white crappie from Brownlee Reservoir at Burnt River exceeded a cancer risk screening value of 10-6 established by the U.S. Environmental Protection Agency. Concentrations of organochlorine compounds in bed sediment were smaller than concentrations in fish tissue. Concentrations of p,p'DDE, the only compound detected in all three bed-sediment samples, ranged from 1.1 micrograms per kilogram dry weight in C.J. Strike Reservoir to 11 micrograms per kilogram dry weight in Brownlee Reservoir at Burnt River. Data from this study, compared with data collected in the upper Snake River Basin from 1992 to 1994, indicates that, in general, organochlorine concentrations in fish tissue and bed sediment increased from the headwaters of the Snake River in Wyoming downstream to Brownlee Reservoir. The largest trace-element concentrations in fish tissue were in liver samples from carp from Brownlee Reservoir at Burnt River and suckers from the Boise River near Twin Springs. Concentrations of most trace elements were larger in livers than in the sport- fish fillets. However, mercury concentrations were generally larger in the sportfish fillets; they ranged from 0.08 microgram per gram wet weight in yellow perch from C.J. Strike Reservoir to 0.32 microgram per gram wet weight in channel catfish from Brownlee Reservoir at Burnt River. None of the trace-element concentrations in fillets exceeded median international standards or U.S. Food and Drug Administration action levels. Large trace-element concentrations in the upper Snake River Basin were reported in liver samples from suckers from headwater streams, probably a result of historical mining and weathering of metal-rich rocks. Concentrations of most trace elements in the bed-sediment samples were largest in Brownlee Reservoir at Mountain Man Lodge. Concentrations of arsenic, cadmium, chromium, copper, nickel, and zinc in bed sediment from the Mountain Man Lodge site exceeded either the threshold effect level or probable effect level established by the Canadian Government for the protection of benthic life. Arsenic, chromium, copper, and nickel concentrations in bed sediment from Brownlee Reservoir at Burnt River and chromium, copper, and nickel in bed sediment from C.J. Strike Reservoir also exceeded the threshold effect level.

Angiogenic effects of borate glass microfibers in a rodent model.

PubMed

Lin, Yinan; Brown, Roger F; Jung, Steven B; Day, Delbert E

2014-12-01

The primary objective of this research was to evaluate the use of bioactive borate-based glass microfibers for angiogenesis in soft tissue repair applications. The effect of these fibers on growth of capillaries and small blood vessels was compared to that of 45S5 silica glass microfibers and sham implant controls. Compressed mats of three types of glass microfibers were implanted subcutaneously in rats and tissues surrounding the implant sites histologically evaluated 2-4 weeks post surgery. Bioactive borate glass 13-93B3 supplemented with 0.4 wt % copper promoted extensive angiogenesis as compared to silica glass microfibers and sham control tissues. The angiogenic responses suggest the copper-containing 13-93B3 microfibers may be effective for treating chronic soft tissue wounds. A second objective was to assess the possible systemic cytotoxicity of dissolved borate ions and other materials released from implanted borate glass microfibers. Cytotoxicity was assessed via histological evaluation of kidney tissue collected from animals 4 weeks after subcutaneously implanting high amounts of the borate glass microfibers. The evaluation of the kidney tissue from these animals showed no evidence of chronic histopathological changes in the kidney. The overall results indicate the borate glass microfibers are safe and effective for soft tissue applications. © 2014 Wiley Periodicals, Inc.

Effects of Cuminum cyminum L. essential oil on some epididymal sperm parameters and histopathology of testes following experimentally induced copper poisoning in mice.

PubMed

Sakhaee, E; Emadi, L; Azari, O; Kheirandish, R; Esmaili Nejad, M R; Shafiei Bafti, H

2016-06-01

Copper overload can cause sperm cell damage by inducing oxidative stress. On the other hand, cumin has a good antioxidant potential. Therefore, the aim of this study was to evaluate the effects of cumin on sperm quality and testicular tissue following experimentally induced copper poisoning in mice. Forty-eight mature male mice were divided into four equal groups as follows: group Cu which received 0.1 ml copper sulphate at dose of 100 mg kg(-1) , group Cc which received Cuminum cyminum at dose of 1 mg kg(-1) , treatment group which received copper sulphate (100 mg kg(-1) ) and treated with Cuminum cyminum (1 mg kg(-1) ), and control group which received the same volume of normal saline. Six mice in each group were sacrificed at week 4 and week 6. The results showed that sperm concentration, motility and viability in group Cu were significantly decreased at weeks 4 and 6, and severe degenerative changes were observed in testicular tissues in comparison with the control group. In treatment group, significant improvement in the sperm count, motility and viability, and normal architecture in most seminiferous tubules with organised epithelium was observed compared to the group Cu. The sperm quality parameters in the treatment group approached those of the control group. © 2015 Blackwell Verlag GmbH.

The Features of Copper Metabolism in the Rat Liver during Development

PubMed Central

2015-01-01

Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed. In the late weaning, the ETCM switches to the adult type copper metabolism (ATCM), which is manifested by the unlocking of copper excretion and the induction of ceruloplasmin gene activity. The considerable progress has been made in the understanding of the molecular basis of copper metabolic turnover in the ATCM, but many aspects of the copper homeostasis in the ETCM remain unclear. The aim of this study was to investigate the copper metabolism during transition from the ETCM (up to 12-days-old) to the ATCM in the rats. It was shown that in the liver, copper was accumulated in the nuclei during the first 5 days of life, and then it was re-located to the mitochondria. In parallel with the mitochondria, copper bulk bound with cytosolic metallothionein was increased. All compartments of the liver cells rapidly lost most of their copper on the 13th day of life. In newborns, serum copper concentration was low, and its major fraction was associated with holo-Cp, however, a small portion of copper was bound to extracellular metallothionein and a substance that was slowly eluted during gel-filtration. In adults, serum copper concentration increased by about a factor of 3, while metallothionein-bound copper level decreased by a factor of 2. During development, the expression level of Cp, Sod1, Cox4i1, Atp7b, Ctr1, Ctr2, Cox17, and Ccs genes was significantly increased, and metallothionein was decreased. Atp7a gene’s activity was fully repressed. The copper routes in newborns are discussed. PMID:26474410

Metals uptake and health risks associated with cattle grazing on mine tailings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuji, J.S.

1994-12-31

Cattle are used at a site in Arizona to revegetate mine tailings dams by dispersing seeds and adding fertilizer with their manure. Although this program has been successful in revegetating the slopes, the residual metals in the tailings may potentially be accumulated by the cattle. Using US EPA guidelines on indirect exposure pathways and data on metals in tailings and in grasses, exposure and tissue levels of metals were calculated to assess health threats to the cattle or to those consuming the beef. Lead in the tailings and cadmium in tailings and grasses were selected for detailed exposure analysis viamore » ingestion of tailings and grasses by grazing cattle. Predicted exposures to cattle were below levels resulting in toxic effects to livestock. Estimated human exposures were below the EPA reference dose for cadmium even for a 15 kg child consuming beef or beef liver. Similarly, estimated tissue levels of lead were within reported background dietary levels of lead in beef and kidney. Necropsies of four newborn calves found no evidence of metal toxicity, but possible copper and selenium deficiencies combined with viral infection. Similarly, blood samples from pregnant cattle had non-detectable levels of lead, arsenic, and cadmium.« less

Sublethal effect of copper toxicity against histopathological changes in the spiny lobster, Panulirus homarus (Linnaeus, 1758).

PubMed

Maharajan, A; Rajalakshmi, S; Vijayakumaran, M; Kumarasamy, P

2012-02-01

The tissue damage induced by various organic pollutants in aquatic animals is well documented, but there is a dearth of information relating to the histological alterations induced by copper in the spiny lobster. In the present study, intermoult juveniles of the spiny lobster Panulirus homarus (average weight 150-200 g) were exposed to two sublethal concentrations of the copper (9.55 and 19.1 μg/l) for a period of 28 days. The muscle, hepatopancreas, midgut, gills, thoracic ganglion and heart of the lobsters were then dissected out and processed for light microscopic studies. Exposure to copper was found to result in several alterations in the histoarchitecture of the muscle, hepatopancreas, midgut, gills, thoracic ganglion and heart of P. homarus. The alterations included disruption and congestion of muscle bundle in muscle tissue; blackened haemocytes; distended lumen and F cell; necrosis of the tubules of the hepatopancreas; disarrangement of circular muscle of the midgut; accumulation of haemocytes in the haemocoelic space; swelling and fusion of lamellae; abnormal gill tips; hyperplastic, necrotic, and blackened secondary gill lamellae of the gills; damaged neurosecretory cell and sensory and motor fibre; necrotic of the thoracic ganglion; dispersedly arranged muscle bands; clumped satellite cells and nucleus of the heart. The results obtained suggest that the muscle, hepatopancreas, midgut, gills, thoracic ganglion and heart of lobsters exposed to copper were structurally altered. Such alterations could affect vital physiological functions, such as absorption, storage and secretion of the hepatopancreas, digestion of gut and respiration, osmotic and ionic regulations of the gills, which in turn could ultimately affect the survival and growth of P. homarus. Thus, all possible remedial measures should be adopted to prevent the occurrence of copper contamination in the aquatic environment.

Combining -Omics to Unravel the Impact of Copper Nutrition on Alfalfa (Medicago sativa) Stem Metabolism.

PubMed

Printz, Bruno; Guerriero, Gea; Sergeant, Kjell; Audinot, Jean-Nicolas; Guignard, Cédric; Renaut, Jenny; Lutts, Stanley; Hausman, Jean-Francois

2016-02-01

Copper can be found in the environment at concentrations ranging from a shortage up to the threshold of toxicity for plants, with optimal growth conditions situated in between. The plant stem plays a central role in transferring and distributing minerals, water and other solutes throughout the plant. In this study, alfalfa is exposed to different levels of copper availability, from deficiency to slight excess, and the impact on the metabolism of the stem is assessed by a non-targeted proteomics study and by the expression analysis of key genes controlling plant stem development. Under copper deficiency, the plant stem accumulates specific copper chaperones, the expression of genes involved in stem development is decreased and the concentrations of zinc and molybdenum are increased in comparison with the optimum copper level. At the optimal copper level, the expression of cell wall-related genes increases and proteins playing a role in cell wall deposition and in methionine metabolism accumulate, whereas copper excess imposes a reduction in the concentration of iron in the stem and a reduced abundance of ferritins. Secondary ion mass spectrometry (SIMS) analysis suggests a role for the apoplasm as a copper storage site in the case of copper toxicity. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

Combining -Omics to Unravel the Impact of Copper Nutrition on Alfalfa (Medicago sativa) Stem Metabolism

PubMed Central

Printz, Bruno; Guerriero, Gea; Sergeant, Kjell; Audinot, Jean-Nicolas; Guignard, Cédric; Renaut, Jenny; Lutts, Stanley; Hausman, Jean-Francois

2016-01-01

Copper can be found in the environment at concentrations ranging from a shortage up to the threshold of toxicity for plants, with optimal growth conditions situated in between. The plant stem plays a central role in transferring and distributing minerals, water and other solutes throughout the plant. In this study, alfalfa is exposed to different levels of copper availability, from deficiency to slight excess, and the impact on the metabolism of the stem is assessed by a non-targeted proteomics study and by the expression analysis of key genes controlling plant stem development. Under copper deficiency, the plant stem accumulates specific copper chaperones, the expression of genes involved in stem development is decreased and the concentrations of zinc and molybdenum are increased in comparison with the optimum copper level. At the optimal copper level, the expression of cell wall-related genes increases and proteins playing a role in cell wall deposition and in methionine metabolism accumulate, whereas copper excess imposes a reduction in the concentration of iron in the stem and a reduced abundance of ferritins. Secondary ion mass spectrometry (SIMS) analysis suggests a role for the apoplasm as a copper storage site in the case of copper toxicity. PMID:26865661

Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice

PubMed Central

Matak, Pavle; Zumerle, Sara; Mastrogiannaki, Maria; El Balkhi, Souleiman; Delga, Stephanie; Mathieu, Jacques R. R.; Canonne-Hergaux, François; Poupon, Joel; Sharp, Paul A.; Vaulont, Sophie; Peyssonnaux, Carole

2013-01-01

Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes. How systemic copper status regulates iron absorption is unknown. Mice were subjected to a nutritional copper deficiency-induced anemia regime from birth and injected with copper sulphate intraperitoneally to correct the anemia. Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia inducible factor 2α (HIF-2α) levels, a regulator of iron absorption. HIF-2α upregulation in copper deficiency appeared to be independent of duodenal iron or copper levels and correlated with the expression of iron transporters (Ferroportin - Fpn, Divalent Metal transporter – Dmt1) and ferric reductase – Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper injection resulted in down regulation of HIF-2α-regulated iron absorption genes in the gut. Our work identifies HIF-2α as an important regulator of iron transport machinery in copper deficiency. PMID:23555700

Water Quality Conditions in the Missouri River Mainstem System: 2008 Report

DTIC Science & Technology

2009-09-01

aluminum, arsenic, cadmium , chromium, copper, cyanide, lead, nickel, selenium, silver, and zinc . The acute and chronic water quality standards criteria for... adipose , etc.) tend to accumulate toxicants at different rates. Therefore, when used as an indicator, fish tissue analysis typically uses whole...for metals (i.e., cadmium , chromium, copper, lead, nickel, silver, and zinc ) are based on hardness. Criteria shown for those metals were calculated

Stabilisation of cables of fibronectin with micromolar concentrations of copper: in vitro cell substrate properties.

PubMed

Ahmed, Zubair; Briden, Anita; Hall, Susan; Brown, Robert A

2004-02-01

We have previously described the production of large cables of fibronectin, a large extracellular matrix cell adhesion glycoprotein, which has a potential application in tissue engineering. Here we have stabilised these cables for longer survival and looked at their ultrastructural cell-substrate behaviour in vitro. Dissolution experiments showed that low concentrations of copper not only caused significant material stabilisation but left pores which could promote cell ingrowth, as we have previously reported with Fn-mats. Indeed, the greatest amount of cell ingrowth was observed for copper treated cables. Immunostaining showed S-100(+) multi-layers of cells around the edge of cables while ultrastructural analysis confirmed the presence of a mixture of fibroblasts and bipolar cells associated with fragments of basal lamina, which is a Schwann cell phenotype. Interestingly, the outermost layers of cells consisted of S-100(-) cells, presumed fibroblasts, apparently 'capping' the Schwann cells. Toxicity tests revealed that Schwann cells were only able to grow at the lowest concentration of copper used (1microM) while fibroblasts grew at all concentrations tested. These results could be used to design biomaterials with optimum properties for promoting cellular ingrowth and survival in tissue engineered grafts which may be used to improve peripheral nerve repair.

Comparison of the effect of dietary copper nanoparticles and one copper (II) salt on the copper biodistribution and gastrointestinal and hepatic morphology and function in a rat model

PubMed Central

Ognik, Katarzyna; Fotschki, Bartosz; Zduńczyk, Zenon

2018-01-01

The aim of the study was to investigate the effect of two forms (CuCO3 (CuS); and Cu nanoparticles (CuNP)) and dosages (standard 6.5 mg/kg (H), half of the standard (L)) of additional dietary Cu administered to growing rats on gastrointestinal and hepatic function and morphology. Copper in the form of CuNP vs CuS caused lower Cu faecal/urinal excretion and increased Cu accumulation in the brain tissue. Hepatic high-grade hydropic degeneration and necrotic lesions were observed only in the CuNP-H animals. In the lower gut, the dietary application of CuNP stifled bacterial enzymatic activity of caecal gut microbiota and resulted in lower SCFA production. That diminishing effect of CuNP on caecal microbiota activity was accompanied by a relative increase in the secretion of glycoside hydrolases by bacterial cells. The results showed that in comparison to Cu from CuCO3, Cu nanoparticles to a greater extent were absorbed from the intestine, accumulated in brain tissue, exerted antimicrobial effect in the caecum, and at higher dietary dose caused damages in the liver of rats. PMID:29758074

Copper retention, calcium release and ultrastructural evidence indicate specific Cuprolinic Blue uptake and peculiar modifications in mineralizing aortic valves.

PubMed

Ortolani, F; Tubaro, F; Petrelli, L; Gandaglia, A; Spina, M; Marchini, M

2002-01-01

Previously, reactions with copper phthalocyanines at 0.05 M critical electrolyte concentration were found to cause demineralization in calcifying porcine aortic valves after subdermal implantation in rat, as well as simultaneous visualization of peculiar phthalocyanine-positive layers around cells and cell-derived matrix vesicles. In the present investigation, an appraisal was made of the mechanism and specificity of reactions with Cuprolinic Blue by comparing quantitatively calcium release and copper retention by calcified aortic valves reacted with this phthalocyanine under different critical electrolyte concentration conditions, and the corresponding ultrastructural patterns. It was found that (i) decalcifying properties are inversely proportional to salt molarity; (ii) reactivity to Cuprolinic Blue is critical electrolyte concentration-dependent, since the greatest copper retention occurred in 0.05 M critical electrolyte concentration Cuprolinic Blue-reacted samples, the only ones that also exhibited phthalocyanine-positive layers; (iii) the appearance of phthalocyanine-positive layers depends on Cuprolinic Blue uptake, revealing pericellular clustering of calcium-binding, anionic molecules; and (iv) minor Cuprolinic Blue uptake occurs by residual proteoglycans which still remain in the extracellular matrix after 6-week-long subdermal implantation. The present results indicate that this method is appropriate for the study of mineralized tissues and illustrate peculiar tissue modifications occurring at least in the experimental conditions used here.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wunderle, K; Wayne State University School of Medicine, Detroit, MI; Godley, A

Purpose: The purpose of this investigation is to characterize and quantify X-ray beam profiles for fluoroscopic x-ray beam spectra incorporating spectral (copper) filtration. Methods: A PTW (Freiburg, Germany) type 60016 silicon diode detector and PTW MP3 water tank were used to measure X-ray beam profiles for 60, 80, 100 and 120 kVp x-ray beams at five different copper filtration thicknesses ranging from 0–0.9 mm at 22 and 42 cm fields of view and depths of 1, 5, and 10 cm in both the anode-cathode axis (inplane) and cross-plane directions. All measurements were acquired on a Siemens (Erlangen, Germany) Artis ZeeGomore » fluoroscope inverted from the typical orientation providing an x-ray beam originating from above the water surface with the water level set at 60 cm from the focal spot. Results: X-ray beam profiles for beam spectra without copper filtration compared well to previously published data by Fetterly et al. [Med Phys, 28, 205 (2001)]. Our data collection benefited from the geometric orientation of the fluoroscope, providing a beam perpendicular to the tank water surface, rather than through a thin side wall as did the previously mentioned study. Profiles for beams with copper filtration were obtained which have not been previously investigated and published. Beam profiles in the anode-cathode axis near the surface and at lower x-ray energy exhibited substantial heel effect, which became less pronounced at greater depth. At higher energy with copper filtration in the beam, the dose falloff out-of-field became less pronounced, as would be anticipated given higher scatter photon energy. Conclusion: The x-ray beam profile data for the fluoroscopic x-ray beams incorporating copper filtration are intended for use as reference data for estimating doses to organs or soft tissue, including fetal dose, involving similar beam qualities or for comparison with mathematical models.« less

Replacement of a cytosolic copper/zinc superoxide dismutase by a novel cytosolic manganese superoxide dismutase in crustaceans that use copper (haemocyanin) for oxygen transport.

PubMed Central

Brouwer, Marius; Hoexum Brouwer, Thea; Grater, Walter; Brown-Peterson, Nancy

2003-01-01

The blue crab, Callinectes sapidus, which uses the copper-dependent protein haemocyanin for oxygen transport, lacks the ubiquitous cytosolic copper-dependent enzyme copper/zinc superoxide dismutase (Cu,ZnSOD) as evidenced by undetectable levels of Cu,ZnSOD activity, protein and mRNA in the hepatopancreas (the site of haemocyanin synthesis) and gills. Instead, the crab has an unusual cytosolic manganese SOD (cytMnSOD), which is retained in the cytosol, because it lacks a mitochondrial transit peptide. A second familiar MnSOD is present in the mitochondria (mtMnSOD). This unique phenomenon occurs in all Crustacea that use haemocyanin for oxygen transport. Molecular phylogeny analysis suggests the MnSOD gene duplication is as old as the origin of the arthropod phylum. cytMnSOD activity in the hepatopancreas changes during the moulting cycle of the crab. Activity is high in intermoult crabs and non-detectable in postmoult papershell crabs. mtMnSOD is present in all stages of the moulting cycle. Despite the lack of cytCu,ZnSOD, crabs have an extracellular Cu,ZnSOD (ecCu,ZnSOD) that is produced by haemocytes, and is part of a large, approx. 160 kDa, covalently-linked protein complex. ecCu,ZnSOD is absent from the hepatopancreas of intermoult crabs, but appears in this tissue at premoult. However, no ecCu,ZnSOD mRNA can be detected, suggesting that the protein is recruited from the haemolymph. Screening of different taxa of the arthropod phylum for Cu,ZnSOD activity shows that those crustaceans that use haemoglobin for oxygen transport have retained cytCu,ZnSOD. It appears, therefore, that the replacement of cytCu,ZnSOD with cytMnSOD is part of an adaptive response to the dynamic, haemocyanin-linked, fluctuations in copper metabolism that occur during the moulting cycle of the crab. PMID:12769817

Response to excess copper in the hyperthermophile Sulfolobus solfataricus strain 98/2

PubMed Central

Villafane, Aramis; Voskoboynik, Yekaterina; Cuebas, Mariola; Ruhl, Ilona; Bini, Elisabetta

2009-01-01

Copper is an essential micronutrient, but toxic in excess. Sulfolobus solfataricus cells have the ability to adapt to fluctuations of copper levels in their external environment. To better understand the molecular mechanism behind the organismal response to copper, the expression of the cluster of genes copRTA, which encodes the copper-responsive transcriptional regulator CopR, the copper-binding protein CopT, and CopA, has been investigated and the whole operon has been shown to be cotranscribed at low levels from the copR promoter under all conditions, whereas increased transcription from the copTA promoter occurs in the presence of excess copper. Furthermore, the expression of the copper-transporting ATPase CopA over a 27-hour interval has been monitored by quantitative real-time RT-PCR and compared to the pattern of cellular copper accumulation, as determined in a parallel analysis by Inductively Coupled Plasma Optical Emission spectrometry (ICP-OES). The results provide the basis for a model of the molecular mechanisms of copper homeostasis in Sulfolobus, which relies on copper efflux and sequestration. PMID:19427833

Flux of heavy metal accumulation in various organs of the intertidal marine blue crab, Portunus pelagicus (L.) from the Kuwait coast after the Gulf War.

PubMed

Al-Mohanna, S Y; Subrahmanyam, M N

2001-10-01

The metal levels of arsenic, chromium, copper, lead, magnesium, manganese, selenium, vanadium, and zinc concentrations were determined in various body organs, viz., hepatopancreas, gills, gonad, gastric stomach, and muscle of the blue crab, Portunus pelagicus (Crustacea: Decapoda) to assess the bioaccumulation of metals associated with petroleum input a decade after the 1991 Gulf War oil spillage. Sample solutions prepared were analyzed using an atomic absorption spectrophotometry. High concentrations of Zn and Cu in the muscle and hepatopancreas tissues were a strong indicative of high exposure of P. pelagicus to these metals. However, muscle tissue had been found to accumulate the highest values for all metal speciations analyzed. Copper, zinc, and chromium in samples collected from Station II covering the Kuwait City area were often in excess of those present in Station I and III. Arsenic, lead, magnesium, manganese, selenium, and vanadium were greater in individuals obtained from Station I. A significant correlation was found to exist between Se and V in crab muscle with a surge in Se metal concentration, which was found to be inversely proportional to that of V metal concentration irrespective of the sex of the crab. The difference in patterns of metal occurrence and the significant increase in the Cu and Zn concentrations in various organs of the crab were largely associated with the 1991 Gulf War oil spill. Such results could be used as a baseline for the monitoring of the level of metals in marine organisms of future studies.

Effects of manufactured nano-copper on copper uptake, bioaccumulation and enzyme activities in cowpea grown on soil substrate.

PubMed

Ogunkunle, Clement O; Jimoh, Mahboob A; Asogwa, Nnaemeka T; Viswanathan, K; Vishwakarma, Vinita; Fatoba, Paul O

2018-07-15

Increased use of nanoparticles-based products in agriculture portends important implications for agriculture. Therefore, the impact of nano-copper particles (<25 nm and 60-80 nm) on Cu uptake, bioaccumulation (roots, leaves and seeds), activity of ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and lipid peroxidation in leaves and roots of Vigna unguiculata (cowpea) was studied. Plants were exposed to four levels (0, 125, 500 and 1000 mg/kg) of 25 nm or 60-80 nm nano-Cu for 65 days. Results indicated significant (P<.05) uptake of Cu at all nano-Cu levels compared to control, and bioaccumulation increased in seeds by at least 250%. Response of antioxidant enzymes to both nano-Cu types was concentration-dependent. Activity of APX and GR was enhanced in leaves and roots in response to both nano-Cu treatments in similar patterns compared to control. Both nano-Cu increased CAT activity in roots while SOD activity reduced in both leaves and roots. This shows that response of antioxidant enzymes to nano-Cu toxicity was organ-specific in cowpea. Malondialdehyde, a measure of lipid peroxidation, increased at 500 -1000 mg/kg of 25 nm nano-Cu in leaves by average of 8.4%, and 60-80 nm nano-Cu in root by 52.8%, showing particle-size and organ-dependent toxicity of nano-Cu. In conclusion, exposure of cowpea to nano-Cu treatments increased both the uptake and bioaccumulation of Cu, and also promoted the activity of APX and GR in root and leaf tissues of cowpea. Therefore, APX- and GR-activity level could be a useful predictive biomarker of nano-Cu toxicity in cowpea. Copyright © 2018 Elsevier Inc. All rights reserved.

Copper Tolerance and Biosorption of Saccharomyces cerevisiae during Alcoholic Fermentation

PubMed Central

Liu, Ling-ling; Jia, Bo; Zhao, Fang; Huang, Wei-dong; Zhan, Ji-cheng

2015-01-01

At high levels, copper in grape mash can inhibit yeast activity and cause stuck fermentations. Wine yeast has limited tolerance of copper and can reduce copper levels in wine during fermentation. This study aimed to understand copper tolerance of wine yeast and establish the mechanism by which yeast decreases copper in the must during fermentation. Three strains of Saccharomyces cerevisiae (lab selected strain BH8 and industrial strains AWRI R2 and Freddo) and a simple model fermentation system containing 0 to 1.50 mM Cu2+ were used. ICP-AES determined Cu ion concentration in the must decreasing differently by strains and initial copper levels during fermentation. Fermentation performance was heavily inhibited under copper stress, paralleled a decrease in viable cell numbers. Strain BH8 showed higher copper-tolerance than strain AWRI R2 and higher adsorption than Freddo. Yeast cell surface depression and intracellular structure deformation after copper treatment were observed by scanning electron microscopy and transmission electron microscopy; electronic differential system detected higher surface Cu and no intracellular Cu on 1.50 mM copper treated yeast cells. It is most probably that surface adsorption dominated the biosorption process of Cu2+ for strain BH8, with saturation being accomplished in 24 h. This study demonstrated that Saccharomyces cerevisiae strain BH8 has good tolerance and adsorption of Cu, and reduces Cu2+ concentrations during fermentation in simple model system mainly through surface adsorption. The results indicate that the strain selected from China’s stress-tolerant wine grape is copper tolerant and can reduce copper in must when fermenting in a copper rich simple model system, and provided information for studies on mechanisms of heavy metal stress. PMID:26030864

Beneficial effects of virgin coconut oil on lipid parameters and in vitro LDL oxidation.

PubMed

Nevin, K G; Rajamohan, T

2004-09-01

The present study was conducted to investigate the effect of consumption of virgin coconut oil (VCO) on various lipid parameters in comparison with copra oil (CO). In addition, the preventive effect of polyphenol fraction (PF) from test oils on copper induced oxidation of LDL and carbonyl formation was also studied. After 45 days of oil feeding to Sprague-Dawley rats, several lipid parameters and lipoprotein levels were determined. PF was isolated from the oils and its effect on in vitro LDL oxidation was assessed. VCO obtained by wet process has a beneficial effect in lowering lipid components compared to CO. It reduced total cholesterol, triglycerides, phospholipids, LDL, and VLDL cholesterol levels and increased HDL cholesterol in serum and tissues. The PF of virgin coconut oil was also found to be capable of preventing in vitro LDL oxidation with reduced carbonyl formation. The results demonstrated the potential beneficiary effect of virgin coconut oil in lowering lipid levels in serum and tissues and LDL oxidation by physiological oxidants. This property of VCO may be attributed to the biologically active polyphenol components present in the oil.

The prevalence of low serum zinc and copper levels and dietary habits associated with serum zinc and copper in 12- to 36-month-old children from low-income families at risk for iron deficiency.

PubMed

Schneider, Julie M; Fujii, Mary L; Lamp, Catherine L; Lönnerdal, Bo; Zidenberg-Cherr, Sheri

2007-11-01

Iron and zinc share common food sources, and children at risk of iron deficiency may also develop zinc deficiency. We determined the prevalence of zinc and copper deficiency and examined factors associated with serum zinc and copper in young children from low-income families at risk of iron deficiency. A cross-sectional study design was used to assess serum zinc and copper, along with an interview-assisted survey to assess factors associated with serum zinc and copper in a convenience sample. Participants were 435 children aged 12 to 36 months recruited from select clinics of the Special Supplemental Nutrition Program for Women, Infants, and Children in Contra Costa and Tulare Counties, California. Frequencies were used to report prevalence. Multiple linear regressions were conducted to examine factors associated with serum zinc and copper, controlling for age, sex, and ethnicity. The prevalence of low serum zinc level (<70 microg/dL [<10.7 micromol/L]) was 42.8%, and low serum copper level (<90 microg/dL [<14.2 micromol/L]) was <1%. Mean+/-standard deviation of serum copper was 150+/-22 microg/dL (23.6+/-3.5 micromol/L) and 140+/-24 microg/dL (22.1+/-3.8 micromol/L) for anemic and non-anemic children, respectively (t test, P=0.026). In multiple linear regression consumption of sweetened beverages was negatively associated with serum zinc level, and consumption of >15 g/day meat was positively associated with serum zinc level, whereas current consumption of breast milk and >15 g/day beans were positively associated with serum copper level. The prevalence of low serum zinc concentration in the sample was high, and warrants further investigation amongst vulnerable populations.

How do anthropogenic contaminants (ACs) affect behaviour? Multi-level analysis of the effects of copper on boldness in hermit crabs.

PubMed

White, Stephen J; Briffa, Mark

2017-02-01

Natural animal populations are increasingly exposed to human impacts on the environment, which could have consequences for their behaviour. Among these impacts is exposure to anthropogenic contaminants. Any environmental variable that influences internal state could impact behaviour across a number of levels: at the sample mean, at the level of among-individual differences in behaviour ('animal personality') and at the level of within-individual variation in behaviour (intra-individual variation, 'IIV'). Here we examined the effect of exposure to seawater-borne copper on the startle response behaviour of European hermit crabs, Pagurus bernhardus across these levels. Copper exposure rapidly led to longer startle responses on average, but did not lead to any change in repeatability indicating that individual differences were present and equally consistent in the presence and absence of copper. There was no strong evidence that copper exposure led to changes in IIV. Our data show that exposure to copper for 1 week produces sample mean level changes in the behaviour of hermit crabs. However, there is no evidence that this exposure led to changes in repeatability through feedback loops.

Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hao; Zhang, Yikai; Zheng, Shanyuan

Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cellsmore » by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities of cisplatin.« less

Heavy metal concentrations in bovine tissues (muscle, liver and kidney) and their relationship with heavy metal contents in consumed feed.

PubMed

Hashemi, Majid

2018-06-15

Toxic (lead, cadmium and mercury) and essential trace (copper and zinc) metals were measured in muscle, liver and kidney samples of bovine and their relationships with heavy metal concentrations in consumed feed were studied. A total of 216 tissue samples from 72 cows and 216 feed samples from 18 farms were collected during four seasons and analyzed for heavy metals by inductively coupled plasma-optical emission spectrometry after wet digestion. The arithmetic mean concentrations (mg/Kg wet weight) of lead (Pb), cadmium (Cd) and mercury were respectively, 0.221, 0.028 and 0.003 in muscle, 0.273, 0.047 and 0.002 in liver and 0.244, 0.114 and 0.003 in kidney. All measured concentrations (with the exception of Pb in muscle) were below the European Union maximum residual limits (MRL). The Cd contents of the kidney were significantly higher than which observed in other tissues. Although, copper (Cu) and zinc (Zn) levels in all of samples were below MRL, but results showed that many cattles may be suffering from Cu and/or Zn deficiency. Significant and positive correlations between Pb (p < 0.05, r = 0.163) and Cd (p < 0.01, r = 0.303) concentrations in feed and studied organs were observed. As a considerable amount of metals above MRL were noticed in our study, continuous monitoring of these metals is recommended to avoid hazardous transfer to human through the food of animal origin. Copyright © 2018 Elsevier Inc. All rights reserved.

Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

PubMed

Stepien, Magdalena; Jenab, Mazda; Freisling, Heinz; Becker, Niels-Peter; Czuban, Magdalena; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Mancini, Francesca Romana; Savoye, Isabelle; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Iqbal, Khalid; Trichopoulou, Antonia; Bamia, Christina; Orfanos, Philippos; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Merino, Susana; Jakszyn, Paula; Sanchez, Maria-Jose; Dorronsoro, Miren; Huerta, José María; Barricarte, Aurelio; Boden, Stina; van Guelpen, Behany; Wareham, Nick; Khaw, Kay-Tee; Bradbury, Kathryn E; Cross, Amanda J; Schomburg, Lutz; Hughes, David J

2017-07-01

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cytoplasmic CopZ-Like Protein and Periplasmic Rusticyanin and AcoP Proteins as Possible Copper Resistance Determinants in Acidithiobacillus ferrooxidans ATCC 23270

PubMed Central

Navarro, Claudio A.; von Bernath, Diego; Martínez-Bussenius, Cristóbal; Castillo, Rodrigo A.

2015-01-01

Acidophilic organisms, such as Acidithiobacillus ferrooxidans, possess high-level resistance to copper and other metals. A. ferrooxidans contains canonical copper resistance determinants present in other bacteria, such as CopA ATPases and RND efflux pumps, but these components do not entirely explain its high metal tolerance. The aim of this study was to find other possible copper resistance determinants in this bacterium. Transcriptional expression of A. ferrooxidans genes coding for a cytoplasmic CopZ-like copper-binding chaperone and the periplasmic copper-binding proteins rusticyanin and AcoP, which form part of an iron-oxidizing supercomplex, was found to increase when the microorganism was grown in the presence of copper. All of these proteins conferred more resistance to copper when expressed heterologously in a copper-sensitive Escherichia coli strain. This effect was absent when site-directed-mutation mutants of these proteins with altered copper-binding sites were used in this metal sensitivity assay. These results strongly suggest that the three copper-binding proteins analyzed here are copper resistance determinants in this extremophile and contribute to the high-level metal resistance of this industrially important biomining bacterium. PMID:26637599

Synthetic fluorescent probes for studying copper in biological systems

PubMed Central

Cotruvo, Joseph A.; Aron, Allegra T.; Ramos-Torres, Karla M.; Chang, Christopher J.

2015-01-01

The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues. Whereas copper and other transition metal ions are commonly thought of as static cofactors buried within protein active sites, emerging data points to the presence of additional loosely bound, labile pools that can participate in dynamic signalling pathways. Against this backdrop, we review advances in sensing labile copper pools and understanding their functions using synthetic fluorescent indicators. Following brief introductions to cellular copper homeostasis and considerations in sensor design, we survey available fluorescent copper probes and evaluate their properties in the context of their utility as effective biological screening tools. We emphasize the need for combined chemical and biological evaluation of these reagents, as well as the value of complementing probe data with other techniques for characterizing the different pools of metal ions in biological systems. This holistic approach will maximize the exciting opportunities for these and related chemical technologies in the study and discovery of novel biology of metals. PMID:25692243

Synthetic fluorescent probes for studying copper in biological systems.

PubMed

Cotruvo, Joseph A; Aron, Allegra T; Ramos-Torres, Karla M; Chang, Christopher J

2015-07-07

The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues. Whereas copper and other transition metal ions are commonly thought of as static cofactors buried within protein active sites, emerging data points to the presence of additional loosely bound, labile pools that can participate in dynamic signalling pathways. Against this backdrop, we review advances in sensing labile copper pools and understanding their functions using synthetic fluorescent indicators. Following brief introductions to cellular copper homeostasis and considerations in sensor design, we survey available fluorescent copper probes and evaluate their properties in the context of their utility as effective biological screening tools. We emphasize the need for combined chemical and biological evaluation of these reagents, as well as the value of complementing probe data with other techniques for characterizing the different pools of metal ions in biological systems. This holistic approach will maximize the exciting opportunities for these and related chemical technologies in the study and discovery of novel biology of metals.

Copper absorption from human milk, cow's milk, and infant formulas using a suckling rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loennerdal, B.B.; Bell, J.G.; Keen, C.L.

1985-11-01

Since copper deficiency is known to occur during infancy, it becomes important to assess copper uptake from various infant diets. The authors have investigated the uptake of copper from human milk, cow's milk, cow's milk formulas, cereal/milk formula and soy formula, compensating for the decay of /sup 64/Cu and using the suckling rat as a model. Radiocopper was added to the diet in trace amounts. Ultracentrifugation, ultrafiltration, and gel filtration were used to show that the added /sup 64/Cu bound to milk fractions and individual binding compounds in a manner analogous to the distribution of native copper, thus validating themore » use of extrinsically labeled diets. Labeled diets were intubated into 14-day-old suckling rats. Animals were killed after 6 h and tissues removed and counted. Liver copper uptake was 25% from human milk, 23% from cow's milk formula, 18% from cow's milk, 17% from premature (cow's milk based) infant formula, 17% from cereal/milk formula and 10% from soy formula. These results show that the rat pup model may provide a rapid, inexpensive, and sensitive method to assay bioavailability of copper from infant foods.« less

SOLVING A COPPER CORROSION PROBLEM WITH ORTHOPHOSPHATE: INDIAN HILL, OHIO CASE STUDY

EPA Science Inventory

Many small and medium-sized water systems have troublt complying with the copper Action Level (of the Lead and Copper Rule), sometimes concurrently with meeting the lead Action level. The problem is especially troubling and widespread with ground water supplies having high alkali...

The protective effect of 2-mercaptoethane sulfonate (MESNA) against traumatic brain injury in rats.

PubMed

Yilmaz, Erdal Resit; Kertmen, Hayri; Gürer, Bora; Kanat, Mehmet Ali; Arikok, Ata Türker; Ergüder, Berrin Imge; Hasturk, Askin Esen; Ergil, Julide; Sekerci, Zeki

2013-01-01

The agent, 2-mercaptoethane sulfonate (MESNA), is a synthetic small molecule, widely used as a systemic protective agent against chemotherapy toxicity, but is primarily used to reduce hemorrhagic cystitis induced by cyclophosphamide. Because MESNA has potential antioxidant and cytoprotective effects, so we hypothesized that MESNA may protect the brain against traumatic injury. Thirty-two rats were randomized into four groups of eight animals each; Group 1 (sham), Group 2 (trauma), Group 3 (150 mg/kg MESNA), Group 4 (30 mg/kg methylprednisolone). Only skin incision was performed in the sham group. In all the other groups, the traumatic brain injury model was created by an object weighing 450 g falling freely from a height of 70 cm through a copper tube on to the metal disc over the skull. The drugs were administered immediately after the injury. The animals were killed 24 h later. Brain tissues were extracted for analysis, where levels of tissue malondialdehyde, caspase-3, glutathione peroxidase, superoxide dismutase, nitric oxide, nitric oxide synthetase and xanthine oxidase were analyzed. Also, histopathological evaluation of the tissues was performed. After head trauma, tissue malondialdehyde levels increased; these levels were significantly decreased by MESNA administration. Caspase-3 levels were increased after trauma, but no effect of MESNA was determined in caspase-3 activity. Following trauma, both glutathione peroxidase and superoxide dismutase levels were decreased; MESNA increased the activity of both these antioxidant enzymes. Also, after trauma, nitric oxide, nitric oxide synthetase and xanthine oxidase levels were increased; administration of MESNA significantly decreased the levels of nitric oxide, nitric oxide synthetase and xanthine oxidase, promising an antioxidant activity. Histopathological analysis showed that MESNA protected the brain tissues well from injury. Although further studies considering different dose regimens and time intervals are required, MESNA was shown to be at least as effective as methylprednisolone in the traumatic brain injury model.

Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

PubMed

Sata, F; Araki, S; Murata, K; Aono, H

1998-06-12

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il; Shoshani-Dror, Dana; Guillemin, Claire

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy.more » Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and oxidative stress of liver.« less

Gastrointestinal effects associated with soluble and insoluble copper in drinking water.

PubMed Central

Pizarro, F; Olivares, M; Araya, M; Gidi, V; Uauy, R

2001-01-01

The aim of this study was to determine whether total copper or soluble copper concentration is associated with gastrointestinal signs and symptoms. Forty-five healthy adult women (18-55 years of age), living in Santiago, Chile, ingested tap water with 5 mg/L of copper containing different ratios of soluble copper (copper sulfate) and insoluble copper (copper oxide) over a 9-week period. Three randomized sequences of the different copper ratios (0:5, 1:4, 2:3, 3:2, and 5:0 mg/L) were followed. Subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. Mean water consumption was similar among groups. Serum copper levels, ceruloplasmin, and activities of liver enzymes were within normal limits. No differences were detected between the means of biochemical parameters at the beginning and at the end of the study. Twenty subjects presented gastrointestinal disturbances at least once during the study, 9 suffered diarrhea (with or without abdominal pain and vomiting), and the other 11 subjects reported abdominal pain, nausea, or vomiting. No differences were found in incidence of abdominal pain, nausea, vomiting, and diarrhea regardless of the ratio of copper sulfate to copper oxide. In conclusion, both copper sulfate (a soluble compound) and copper oxide (an insoluble compound) have comparable effects on the induction of gastrointestinal manifestations, implying that similar levels of ionic copper were present in the stomach. PMID:11673125

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants.

PubMed

Talat, Mohamed A; Ahmed, Anwar; Mohammed, Lamia

2015-10-01

To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1 ± 3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. The mean zinc level was 60.1 ± 22.6 ug/dl in the cases, and 102.1 ± 18 ug/dl in the controls (p<0.001). The mean copper level was 180.1 ± 32.4 ug/dl in cases compared with 114.5 ± 18.5 ug/dl in controls (p<0.001). Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients.

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

PubMed Central

Talat, Mohamed A.; Ahmed, Anwar; Mohammed, Lamia

2015-01-01

Objective: To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. Methods: A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. Results: The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001). Conclusion: Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients. PMID:26492112

Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers.

PubMed

Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

2013-11-15

Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. To produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (<5% yield). However, they were an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as the background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 μM in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity.

Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth

PubMed Central

Vittorio, Orazio; Brandl, Miriam; Cirillo, Giuseppe; Kimpton, Kathleen; Hinde, Elizabeth; Gaus, Katharina; Yee, Eugene; Kumar, Naresh; Duong, Hien; Fleming, Claudia; Haber, Michelle; Norris, Murray; Boyer, Cyrille; Kavallaris, Maria

2016-01-01

Neuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti-cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran-Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran-Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth. PMID:27374085

CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis

PubMed Central

Marcus, Sarah A.; Sidiropoulos, Sarah W.; Steinberg, Howard; Talaat, Adel M.

2016-01-01

Mycobacterium tuberculosis, a pathogen infecting one third of the world population, faces numerous challenges within the host, including high levels of copper. We have previously shown that M. tuberculosis CsoR is a copper inducible transcriptional regulator. Here we examined the hypothesis that csoR is necessary for maintaining copper homeostasis and surviving under various stress conditions. With an unmarked csoR knockout strain, we were able to characterize the role of csoR in M. tuberculosis as it faced copper and host stress. Growth under high levels of copper demonstrated that M. tuberculosis survives copper stress significantly better in the absence of csoR. Yet under minimal levels of copper, differential expression analysis revealed that the loss of csoR results in a cell wide hypoxia-type stress response with the induction of the DosR regulon. Despite the stress placed on M. tuberculosis by the loss of csoR, survival of the knockout strain was increased compared to wild type during the early chronic stages of mouse infection, suggesting that csoR could play an active role in modulating M. tuberculosis fitness within the host. Overall, analysis of CsoR provided an increased understanding of the M. tuberculosis copper response with implications for other intracellular pathogens harboring CsoR. PMID:26999439

Demystifying Controlling Copper Corrosion

EPA Science Inventory

The LCR systematically misses the highest health and corrosion risk sites for copper. Additionally, there are growing concerns for WWTP copper in sludges and discharge levels. There are many corrosion control differences between copper and lead. This talk explains the sometimes c...

EVALUATING THE IMPACT OF WATER CHEMISTRY ON CUPROSOLVENCY AND COPPER CORROSION BY-PRODUCT USING A SIMPLE COPPER PIPE RECIRCULATING LOOP SYSTEM

EPA Science Inventory

1991, EPA publicized the Lead and Copper Rule (LCR),which set regulations to minimize the amount of lead copper in drinking water. The LCR set the copper action level at 1.3 mg/L in more then 10% of customer’s first-draw taps sampled. Potential health effects of copper include vo...

Inventory of Exposure-Related Data Systems Sponsored By Federal Agencies

DTIC Science & Technology

1992-05-01

Health and Nutrition Examination Survey (NHANES) .... 1-152 National Herbicide Use Database .......................... 1-157 National Human Adipose Tissue ...Human Adipose Tissue ) ..................................... National Hydrologic Benchmark Network (see National Water Quality Networks Programs...Inorganic compounds (arsenic, iron, lead, mercury, zinc , cadmium , chromium, copper); pesticides (1982 and 1987 data available for 35 pesticides; original

Selenium, copper, zinc, iron levels and mortality in patients with sepsis and systemic inflammatory response syndrome in Western Black Sea Region, Turkey.

PubMed

Ayoglu, Hilal; Sezer, Ustun; Akin, Mehmet; Okyay, Dilek; Ayoglu, Ferruh; Can, Murat; Kucukosman, Gamze; Piskin, Ozcan; Aydin, Bengu; Cimencan, Murat; Gur, Abdullah; Turan, Isil

2016-04-01

To evaluate the changing levels of selenium, copper, zinc and iron in patients with sepsis and systemic inflammatory response syndrome and their influence on mortality. The prospective study was conducted at a tertiary care university hospital in Zonguldak city in the western Black Sea region of Turkey from January 2012 to December 2013, and comprised patients with sepsis and systemic inflammatory response syndrome. Blood samples were taken on 1st, 3rd, 5th and 7th days to measure serum selenium, copper, zinc and iron levels. Patients' demographic data, presence of additional diseases and mortality were recorded. Of the 57 patients, 28(49.1%) were female and 29(50.9%) were male, with an overall mean age of 60.3±19.4 years, mean height of 166.1±11.4cm, mean weight of 76.5±17.5kg. Copper and zinc levels were in the normal range, while selenium and iron levels were lower than the limit values at all measuring periods. There was no significant difference between first and other days in accordance with element levels (p>0.05). Baseline copper levels in patients with malignancy were lower than patients without malignancy (p< 0.05). In hypertensive patients, baseline copper levels were higher and 7th day levels were lower than non-hypertensive (p< 0.05). Baseline selenium levels of those who died were lower than the other patients (p< 0.05). Selenium and iron levels were decreased in patients with sepsis-systemic inflammatory response syndrome and copper levels were lower in patients with malignancy, hypertension and chronic obstructive pulmonary disease (p< 0.05). There was no change in zinc levels of the patients. Reduced basal selenium levels of patients with sepsis and systemic inflammatory response syndrome were associated with mortality.

Copper-releasing, boron-containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering.

PubMed

Erol, M M; Mouriňo, V; Newby, P; Chatzistavrou, X; Roether, J A; Hupa, L; Boccaccini, Aldo R

2012-02-01

The aim of this study was to synthesize and characterize new boron-containing bioactive glass-based scaffolds coated with alginate cross-linked with copper ions. A recently developed bioactive glass powder with nominal composition (wt.%) 65 SiO2, 15 CaO, 18.4 Na2O, 0.1 MgO and 1.5 B2O3 was fabricated as porous scaffolds by the foam replica method. Scaffolds were alginate coated by dipping them in alginate solution. Scanning electron microscopy investigations indicated that the alginate effectively attached on the surface of the three-dimensional scaffolds leading to a homogeneous coating. It was confirmed that the scaffold structure remained amorphous after the sintering process and that the alginate coating improved the scaffold bioactivity and mechanical properties. Copper release studies showed that the alginate-coated scaffolds allowed controlled release of copper ions. The novel copper-releasing composite scaffolds represent promising candidates for bone regeneration. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of chronic copper exposure during early life in rhesus monkeys.

PubMed

Araya, Magdalena; Kelleher, Shannon L; Arredondo, Miguel A; Sierralta, Walter; Vial, María Teresa; Uauy, Ricardo; Lönnerdal, Bo

2005-05-01

Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

The effects of copper on blood and biochemical parameters of rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Dethloff, G.M.; Schlenk, D.; Khan, S.; Bailey, H.C.

1999-01-01

Metals are released into aquatic systems from many sources, often at sublethal concentrations. The effects of sublethal concentrations of metals on fish are not entirely understood. The objective of this study was to determine the hematological and biochemical effects of a range of copper concentrations (6.4, 16.0, 26.9 ??g Cu/L) on rainbow trout (Oncorhynchus mykiss) over a prolonged period of time. Trout were exposed to copper, and, at intervals of 3, 7, 14, and 21 days, selected parameters were evaluated. Hemoglobin, hematocrit, plasma glucose, and plasma cortisol levels were elevated in trout exposed to 26.9 ??g Cu/L at day 3 and then returned to levels comparable to control fish. Plasma protein and lactate levels were not significantly altered in trout from any copper treatment. Hepatic copper concentration and hepatic metallothionein mRNA expression were consistently elevated in trout exposed to 26.9 ??g Cu/L. Both of these parameters stabilized by day 3, with only hepatic copper concentration showing a further increase at day 21. Hepatic copper concentration and hepatic metallothionein mRNA expression appear to be robust indicators of copper exposure. Most blood-based parameters evaluated appear to be associated with a transitory, nonspecific stress response. The return of elevated hematological and biochemical parameters to control levels after 3 days and thestabilization of hepatic metallothionein mRNA expression and copper concentration over a similar time period suggested acclimation to dissolved copper at 26.9 ??g/L. Further analysis of the data on blood-based parameters indicated that certain parameters (hemoglobin, hematocrit, plasma glucose, plasma cortisol) may be useful in field monitoring.

Copper and zinc content in wild game shot with lead or non-lead ammunition – implications for consumer health protection

PubMed Central

Sommerfeld, Christine; Müller-Graf, Christine; Selhorst, Thomas; Greiner, Matthias; Gerofke, Antje; Ulbig, Ellen; Gremse, Carl; Spolders, Markus; Schafft, Helmut; Lahrssen-Wiederholt, Monika

2017-01-01

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project “Safety of game meat obtained through hunting” (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition. PMID:28934259

Copper and zinc content in wild game shot with lead or non-lead ammunition - implications for consumer health protection.

PubMed

Schlichting, Daniela; Sommerfeld, Christine; Müller-Graf, Christine; Selhorst, Thomas; Greiner, Matthias; Gerofke, Antje; Ulbig, Ellen; Gremse, Carl; Spolders, Markus; Schafft, Helmut; Lahrssen-Wiederholt, Monika

2017-01-01

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project "Safety of game meat obtained through hunting" (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition.

Low levels of copper reduce the reproductive success of a mobile invertebrate predator.

PubMed

Lee, Ka-Man; Johnston, Emma L

2007-09-01

Marine organisms that occur in urbanised bays can be exposed to low-level chronic pollution that results in sublethal changes to behavior or reproduction. The effects of low levels of copper on the reproductive success of a mobile invertebrate were assessed. Free living flatworms are common predators of bivalves and barnacles. Flatworms (Stylochus pygmaeus) were exposed to low levels of copper ranging from 0 to 25 microg L(-1) in the presence and absence of their barnacle prey (Balanus variegatus). Flatworms laid fewer egg batches when exposed to copper and the hatching success of the eggs was also reduced. Exposure to 25 microg L(-1) copper for 10 d reduced the reproductive success of flatworms by up to 80%. Results were consistent regardless of the presence or absence of prey (barnacles). Barnacles were only moderately affected by copper but exhibited major avoidance behavior (feeding inhibition) in the presence of flatworm predators. This is the first ecotoxicological study on marine flatworms. Experiments are required to quantify the effects of flatworm predator populations on sessile invertebrate community structure in the field.

MicroRNA857 Is Involved in the Regulation of Secondary Growth of Vascular Tissues in Arabidopsis1

PubMed Central

Zhao, Yuanyuan; Lin, Sen; Qiu, Zongbo; Cao, Dechang; Wen, Jialong; Deng, Xin; Wang, Xiaohua; Lin, Jinxing; Li, Xiaojuan

2015-01-01

MicroRNAs (miRNAs) are endogenous small RNAs that repress target gene expression posttranscriptionally, and are critically involved in various developmental processes and responses to environmental stresses in eukaryotes. MiRNA857 is not widely distributed in plants and is encoded by a single gene, AtMIR857, in Arabidopsis (Arabidopsis thaliana). The functions of miR857 and its mechanisms in regulating plant growth and development are still unclear. Here, by means of genetic analysis coupled with cytological studies, we investigated the expression pattern and regulation mechanism of miR857 and its biological functions in Arabidopsis development. We found that miR857 regulates its target gene, Arabidopsis LACCASE7, at the transcriptional level, thereby reducing laccase activity. Using stimulated Raman scattering and x-ray microtomography three-dimensional analyses, we showed that miR857 was involved in the regulation of lignin content and consequently morphogenesis of the secondary xylem. In addition, miR857 was activated by SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 in response to low copper conditions. Collectively, these findings demonstrate the role of miR857 in the regulation of secondary growth of vascular tissues in Arabidopsis and reveal a unique control mechanism for secondary growth based on the miR857 expression in response to copper deficiency. PMID:26511915

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes

PubMed Central

Gordon, Lily D.; Fang, Zhong; Holder, Robert C.; Reid, Sean D.

2015-01-01

ABSTRACT Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. IMPORTANCE Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. PMID:26013489

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes.

PubMed

Young, Christie A; Gordon, Lily D; Fang, Zhong; Holder, Robert C; Reid, Sean D

2015-08-01

Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cytoplasmic CopZ-Like Protein and Periplasmic Rusticyanin and AcoP Proteins as Possible Copper Resistance Determinants in Acidithiobacillus ferrooxidans ATCC 23270.

PubMed

Navarro, Claudio A; von Bernath, Diego; Martínez-Bussenius, Cristóbal; Castillo, Rodrigo A; Jerez, Carlos A

2016-02-15

Acidophilic organisms, such as Acidithiobacillus ferrooxidans, possess high-level resistance to copper and other metals. A. ferrooxidans contains canonical copper resistance determinants present in other bacteria, such as CopA ATPases and RND efflux pumps, but these components do not entirely explain its high metal tolerance. The aim of this study was to find other possible copper resistance determinants in this bacterium. Transcriptional expression of A. ferrooxidans genes coding for a cytoplasmic CopZ-like copper-binding chaperone and the periplasmic copper-binding proteins rusticyanin and AcoP, which form part of an iron-oxidizing supercomplex, was found to increase when the microorganism was grown in the presence of copper. All of these proteins conferred more resistance to copper when expressed heterologously in a copper-sensitive Escherichia coli strain. This effect was absent when site-directed-mutation mutants of these proteins with altered copper-binding sites were used in this metal sensitivity assay. These results strongly suggest that the three copper-binding proteins analyzed here are copper resistance determinants in this extremophile and contribute to the high-level metal resistance of this industrially important biomining bacterium. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The influence of regional geological settings on the seismic hazard level in copper mines in the Legnica-Głogów Copper Belt Area (Poland)

NASA Astrophysics Data System (ADS)

Burtan, Zbigniew

2017-11-01

The current level of rockburst hazard in copper mines of the (LGOM) Legnica- Głogów Copper Belt Area is mostly the consequence of mining-induced seismicity, whilst the majority of rockbursting events registered to date were caused by high-energy tremors. The analysis of seismic readings in recent years reveals that the highest seismic activity among the copper mines in the LGOM is registered in the mine Rudna. This study investigates the seismic activity in the rock strata in the Rudna mine fields over the years 2006-2015. Of particular interest are the key seismicity parameters: the number of registered seismic events, the total energy emissions, the energy index. It appears that varied seismic activity in the area may be the function of several variables: effective mining thickness, the thickness of burst-prone strata and tectonic intensity. The results support and corroborate the view that principal factors influencing the actual seismic hazard level are regional geological conditions in the copper mines within the Legnica-Głogów Copper Belt Area.

Is copper chelation an effective anti-angiogenic strategy for cancer treatment?

PubMed

Antoniades, V; Sioga, A; Dietrich, E M; Meditskou, S; Ekonomou, L; Antoniades, K

2013-12-01

Angiogenesis and the acquisition of an angiogenic phenotype is important for cancer cell proliferation. Copper in an essential trace element that participates in many enzymatic complexes like the cytochrome c, superoxide dismutase and lysyl oxidase and it is involved in processes, like embryogenesis, growth, angiogenesis and carcinogenesis. In particular, its involvement in carcinogenesis was described for the first time in oral submucous fibrosis, where fibroblasts produce large amounts of collagen in the presence of copper. Copper's action in carcinogenesis is two-fold: (1) it participates in reactions with an increased redox potential that result in the production of oxidative products and oxidative stress. Through this mechanism, copper may cause DNA mutations in the nucleus and mitochondria or alterations to membrane phospholipids, (2) it participates in angiogenesis even in the absence of angiogenic molecules, as it was reported for the first time in rabbit cornea models with copolymer pellets charged with PGE1. Copper chelation regimens like penicillamine and tetrathiomolybdate are being described in the literature as having anti-angiogenic, anti-fibrotic and anti-inflammatory actions. Animal models of brain cancer that evaluated the anti-angiogenic properties of copper, have proven evidence of the reduction of tumor's microvascular supply, tumor volume and vascular permeability after plasma copper levels reduction. Interestingly, plasma copper levels reduction was shown to suppress micrometastases generation in mice models of breast cancer. We hypothesize that copper chelation therapy: increases oxidative stress in cancer cells to a level that does not allow survival because of the reduction of anti-oxidative enzymes production. It may also result in inhibition of angiogenesis and of the initiation of the angiogenic switch, because copper normally enhances endothelial cell migration and proliferation, improves binding of growth factors to endothelial cells and enhances the expression of angiogenic molecules. Copper chelation may also reduce extracellular matrix degradation and cancer spread, through reduction of MMP-9 production and probably of other collagenases and may inhibit propagation of micrometastases. However, copper chelation therapy may enhance angiogenesis through reduction of thrombospondin-1, that results into an increase in VEGF-VEGFR2 complexes and a high level of active MMP-9. These hypotheses help in understanding of the anti-angiogenic action of copper chelation therapies and of the complex network of interactions between copper and other molecules involved in angiogenesis. It may also stimulate further research regarding differences in copper metabolism, the effects of anti-copper regimens on organs, the development of resistance, and their possible angiogenic action through thrombospondin expression reduction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

PubMed

Wang, Jianguo; Zhu, Xiaoyan; Guo, Yazhou; Wang, Zhe; Zhao, Baoyu; Yin, Yunhou; Liu, Guowen

2016-07-01

To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

Effects of dietary supplementation with vitamin C and vitamin E and their combination on growth performance, some biochemical parameters, and oxidative stress induced by copper toxicity in broilers.

PubMed

Cinar, Miyase; Yildirim, Ebru; Yigit, A Arzu; Yalcinkaya, Ilkay; Duru, Ozkan; Kisa, Uçler; Atmaca, Nurgul

2014-05-01

This study investigated effects of dietary supplementation with vitamin C, vitamin E on performance, biochemical parameters, and oxidative stress induced by copper toxicity in broilers. A total of 240, 1-day-old, broilers were assigned to eight groups with three replicates of 10 chicks each. The groups were fed on the following diets: control (basal diet), vitamin C (250 mg/kg diet), vitamin E (250 mg/kg diet), vitamin C + vitamin E (250 mg/kg + 250 mg/kg diet), and copper (300 mg/kg diet) alone or in combination with the corresponding vitamins. At the 6th week, the body weights of broilers were decreased in copper, copper + vitamin E, and copper + vitamin C + vitamin E groups compared to control. The feed conversion ratio was poor in copper group. Plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase activities, iron, copper concentrations, and erythrocyte malondialdehyde were increased; plasma vitamin A and C concentrations and erythrocyte superoxide dismutase were decreased in copper group compared to control. Glutathione peroxidase, vitamin C, and iron levels were increased; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and copper levels were decreased in copper + vitamin C group, while superoxide dismutase, glutathione peroxidase, and vitamin E concentrations were increased; aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were decreased in copper with vitamin E group compared to copper group. The vitamin C concentrations were increased; copper, uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and malondialdehyde were decreased in copper + vitamin C + vitamin E group compared to copper group. To conclude, copper caused oxidative stress in broilers. The combination of vitamin C and vitamin E addition might alleviate the harmful effects of copper as demonstrated by decreased lipid peroxidation and hepatic enzymes.

Aberrant expression of copper associated genes after copper accumulation in COMMD1-deficient dogs.

PubMed

Favier, Robert P; Spee, Bart; Fieten, Hille; van den Ingh, Ted S G A M; Schotanus, Baukje A; Brinkhof, Bas; Rothuizen, Jan; Penning, Louis C

2015-01-01

COMMD1-deficient dogs progressively develop copper-induced chronic hepatitis. Since high copper leads to oxidative damage, we measured copper metabolism and oxidative stress related gene products during development of the disease. Five COMMD1-deficient dogs were studied from 6 months of age over a period of five years. Every 6 months blood was analysed and liver biopsies were taken for routine histological evaluation (grading of hepatitis), rubeanic acid copper staining and quantitative copper analysis. Expression of genes involved in copper metabolism (COX17, CCS, ATOX1, MT1A, CP, ATP7A, ATP7B, ) and oxidative stress (SOD1, catalase, GPX1 ) was measured by qPCR. Due to a sudden death of two animals, the remaining three dogs were treated with d-penicillamine from 43 months of age till the end of the study. Presented data for time points 48, 54, and 60 months was descriptive only. A progressive trend from slight to marked hepatitis was observed at histology, which was clearly preceded by an increase in semi-quantitative copper levels starting at 12 months until 42 months of age. During the progression of hepatitis most gene products measured were transiently increased. Most prominent was the rapid increase in the copper binding gene product MT1A mRNA levels. This was followed by a transient increase in ATP7A and ATP7B mRNA levels. In the sequence of events, copper accumulation induced progressive hepatitis followed by a transient increase in gene products associated with intracellular copper trafficking and temporal activation of anti-oxidative stress mechanisms. Copyright © 2014 Elsevier GmbH. All rights reserved.

Talitrid amphipods (Crustacea) as biomonitors for copper and zinc

NASA Astrophysics Data System (ADS)

Rainbow, P. S.; Moore, P. G.; Watson, D.

1989-06-01

Data are presented on the copper and zinc concentrations of four talitrid amphipod species (standard dry weight 10 mg), i.e. Orchestia gammarellus (Pallas), O. mediterranea Costa, Talitrus saltator Montagu and Talorchestia deshayesii (Audouin), from 31 sites in S.W. Scotland, N. Wales and S.W. England. More limited data are also presented for cadmium in O. gammarellus (three sites) and T. deshayesii (one site). In S.W. Scotland, copper concentrations were raised significantly in O. gammarellus from Whithorn and Auchencairn (Solway) and Loch Long and Holy Loch (Clyde). In S.W. England, copper concentrations were highest at Restronguet Creek, Torpoint and Gannel (Cornwall). Samples of O. gammarellus from Islay (inner Hebrides) taken adjacent to the effluent outfalls of local whisky distilleries fell into two groups based on copper concentrations (presumably derived from copper stills), the higher copper levels deriving from the more productive distilleries. High copper levels were found in T. saltator and Tal. deshayesii from Dulas Bay (Wales). Zinc levels in O. gammarellus were high in Holy Loch and Auchencairn (Scotland), Gannel and Torpoint (England) but extremely elevated (as was Zn in O. mediterranea) at Restronguet Creek. Zinc was also high in T. saltator from Dulas Bay (Wales), but not in Tal. deshayesii. Cadmium levels in O. gammarellus from Kilve (Bristol Channel) were much raised. These differences (a) conform with expectations of elevated bioavailability of these metals from well researched areas (S.W. England & N. Wales), and (b) identify hitherto unappreciated areas of enrichment in S.W. Scotland. Orchestia gammarellus is put forward as a suitable biomonitor for copper and zinc in British coastal waters.

LONG-TERM IMPACTS OF ORTHOPHOSPHATE TREATMENT ON COPPER LEVELS - PRESENTATION

EPA Science Inventory

Laboratory, pilot, and field data collected support the theoretical "cupric hydroxide" copper solubility model. For the short time frames inherent in laboratory and pilot studies of copper solubility and in initial field monitoring for the LCR from Tier 1 soldered copper sites, c...

LONG-TERM IMPACTS OF ORTHOPHOSPHATE TREATMENT ON COPPER LEVELS

EPA Science Inventory

Laboratory, pilot, and field data collected support the theoretical “cupric hydroxide” copper solubility model. For the short time frames inherent in laboratory and pilot studies of copper solubility and in initial field monitoring for the LCR from Tier 1 soldered copper sites,...

Induction of micronuclei and binuclei in blood, gill and liver cells of fishes subchronically exposed to cadmium chloride and copper sulphate.

PubMed

Cavas, Tolga; Garanko, Natasha N; Arkhipchuk, Victor V

2005-04-01

Common carp (Cyprinus carpio), Prussian carp (Carassius gibelio) and Peppered cory (Corydoras paleatus) were evaluated as target species to perform genotoxicity tests for heavy metals. Fishes were exposed to different doses of cadmium (0.005-0.1 mg/L) and copper (0.01-0.25 mg/L) for 21 days. Hexavalent chromium at a single dose of 5 mg/L was used as a positive control. Frequencies of micronuclei and binuclei were evaluated comparatively in peripheral blood erythrocytes, gill epithelial cells and liver cells. As a result it was observed that, fish species and their tissues showed differential sensitivity to the heavy metal treatment. In general, frequencies of micronucleated and binucleated cells significantly increased following the exposure for 21 days to copper, cadmium and chromium. On the other hand, gill and liver cells showed higher frequencies of micronuclei and binuclei than erythrocytes. Our results indicated the formation of micronuclei and binuclei in fish cells caused by their exposure to cadmium, copper and chromium, thus verifying results obtained earlier on mammals, which indicated that these heavy metals have cytotoxic and genotoxic effects. The suitability of the micronucleus assay in native fish species for the screening of aquatic genotoxicants is highlighted and the importance of target tissue selection in the piscine micronucleus test is emphasized.

Copper levels and changes in pH induce oxidative stress in the tissue of curimbata (Prochilodus lineatus).

PubMed

Carvalho, Cleoni dos Santos; Bernusso, Vanessa Aline; Fernandes, Marisa Narciso

2015-10-01

We analyzed the effect of exposure to 25% 96 h-LC50 of copper at low (24.5 μg L(-1) Cu, pH 4.5), neutral (7.25 μg L(-1) Cu, pH 7.0) and high pH (4.0 μg L(-1) Cu, pH 8.0) at 20 °C on antioxidant defenses and oxidative stress in the liver, gills and white muscle of the fish Prochilodus lineatus. Water at pH 4.5 and 8.0 affected the enzymatic and non-enzymatic antioxidant systems of the liver and gills, but not of the white muscles of P. lineatus, when compared to water at pH 7.0. After Cu exposure, SOD (superoxide dismutase), GPx (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) activities increased and CAT (catalase) activity decreased in the liver at water at pH 4.5 and 8.0. Meanwhile, the activities of SOD, CAT, GPx, GR and GST increased in the gills at these pHs. SOD and CAT activities increased in the white muscle after Cu exposure at pH 8.0 and GPx, GR and GST activities decreased after Cu exposure at pH 4.5 and 8.0. LPO levels decreased in the liver and gills of fish that were exposed to water at pH 4.5 and 8.0 and, after Cu exposure, the LPO level increased in the liver, gills and white muscle of fish that were exposed to water at pH 4.5 and 8.0, when compared to the control group at pH 7.0. The metallothionein (MT) concentration increased in the liver of fish in water at pH 4.5 and 8.0 and the gill of fish in water at pH 8.0. After Cu exposure, MT in the liver and gills was significantly elevated in fish exposed to water at pH 4.5 and 8.0, but remained at levels similar to the control group in the white muscle. These results indicate a differing sensitivity of fish organs and tissues to essential metals, such as copper, and that toxicity may be relevant at environmental concentrations. These results indicate that the effect of Cu on the response of antioxidant defense systems is determined by water pH. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation.

PubMed

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2015-12-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

PubMed Central

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2016-01-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies. PMID:26587712

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

NASA Astrophysics Data System (ADS)

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2015-12-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.

PubMed

Chen, Yuan; Li, Bin; Zhao, Ran-ran; Zhang, Hui-feng; Zhen, Chao; Guo, Li

2015-04-10

Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Sub-cellular damage by copper in the cnidarian Zoanthus robustus.

PubMed

Grant, A; Trompf, K; Seung, D; Nivison-Smith, L; Bowcock, H; Kresse, H; Holmes, S; Radford, J; Morrow, P

2010-09-01

Sessile organisms may experience chronic exposure to copper that is released into the marine environment from antifoulants and stormwater runoff. We have identified the site of damage caused by copper to the symbiotic cnidarian, Zoanthus robustus (Anthozoa, Hexacorallia). External changes to the zoanthids were apparent when compared with controls. The normally flexible bodies contracted and became rigid. Histological examination of the zoanthid tissue revealed that copper had caused sub-cellular changes to proteins within the extracellular matrix (ECM) of the tubular body. Collagen in the ECM and the internal septa increased in thickness to five and seven times that of controls respectively. The epithelium, which stained for elastin, was also twice as thick and tough to cut, but exposure to copper did not change the total amount of desmosine which is found only in elastin. We conclude that copper stimulated collagen synthesis in the ECM and also caused cross-linking of existing proteins. However, there was no expulsion of the symbiotic algae (Symbiodinium sp.) and no effect on algal pigments or respiration (44, 66 and 110 microg Cu L(-1)). A decrease in net photosynthesis was observed only at the highest copper concentration (156 microg Cu L(-1)). These results show that cnidarians may be more susceptible to damage by copper than their symbiotic algae. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Liver mitochondrial dysfunction and electron transport chain defect induced by high dietary copper in broilers.

PubMed

Yang, Fan; Cao, Huabin; Su, Rongsheng; Guo, Jianying; Li, Chengmei; Pan, Jiaqiang; Tang, Zhaoxin

2017-09-01

Copper is an important trace mineral in the diet of poultry due to its biological activity. However, limited information is available concerning the effects of high copper on mitochondrial dysfunction. In this study, 72 broilers were used to investigate the effects of high dietary copper on liver mitochondrial dysfunction and electron transport chain defect. Birds were fed with different concentrations [11, 110, 220, and 330 mg of copper/kg dry matter (DM)] of copper from tribasic copper chloride (TBCC). The experiment lasted for 60 d. Liver tissues on d 60 were subjected to histopathological observation. Additionally, liver mitochondrial function was recorded on d 12, 36, and 60. Moreover, a site-specific defect in the electron transport chain in liver mitochondria was also identified by using various chemical inhibitors of mitochondrial respiration. The results showed different degrees of degeneration, mitochondrial swelling, and high-density electrons in hepatocytes. In addition, the respiratory control ratio (RCR) and oxidative phosphorylation rate (OPR) in liver mitochondria increased at first and then decreased in high-dose groups. Moreover, hydrogen peroxide (H2O2) generation velocity in treated groups was higher than that in control group, which were magnified by inhibiting electron transport at Complex IV. The results indicated that high dietary copper could decline liver mitochondrial function in broilers. The presence of a site-specific defect at Complex IV in liver mitochondria may be responsible for liver mitochondrial dysfunction caused by high dietary copper. © 2017 Poultry Science Association Inc.

Temporal aspects of copper homeostasis and its crosstalk with hormones

PubMed Central

Peñarrubia, Lola; Romero, Paco; Carrió-Seguí, Angela; Andrés-Bordería, Amparo; Moreno, Joaquín; Sanz, Amparo

2015-01-01

To cope with the dual nature of copper as being essential and toxic for cells, plants temporarily adapt the expression of copper homeostasis components to assure its delivery to cuproproteins while avoiding the interference of potential oxidative damage derived from both copper uptake and photosynthetic reactions during light hours. The circadian clock participates in the temporal organization of coordination of plant nutrition adapting metabolic responses to the daily oscillations. This timely control improves plant fitness and reproduction and holds biotechnological potential to drive increased crop yields. Hormonal pathways, including those of abscisic acid, gibberellins, ethylene, auxins, and jasmonates are also under direct clock and light control, both in mono and dicotyledons. In this review, we focus on copper transport in Arabidopsis thaliana and Oryza sativa and the presumable role of hormones in metal homeostasis matching nutrient availability to growth requirements and preventing metal toxicity. The presence of putative hormone-dependent regulatory elements in the promoters of copper transporters genes suggests hormonal regulation to match special copper requirements during plant development. Spatial and temporal processes that can be affected by hormones include the regulation of copper uptake into roots, intracellular trafficking and compartmentalization, and long-distance transport to developing vegetative and reproductive tissues. In turn, hormone biosynthesis and signaling are also influenced by copper availability, which suggests reciprocal regulation subjected to temporal control by the central oscillator of the circadian clock. This transcriptional regulatory network, coordinates environmental and hormonal signaling with developmental pathways to allow enhanced micronutrient acquisition efficiency. PMID:25941529

40 CFR 141.88 - Monitoring requirements for lead and copper in source water.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the basis of tap samples collected in accordance with § 141.86 shall collect lead and copper source... value or be considered one-half the PQL. (b) Monitoring frequency after system exceeds tap water action level. Any system which exceeds the lead or copper action level at the tap shall collect one source...

Arsenic exposure levels in relation to different working departments in a copper mining and smelting plant

NASA Astrophysics Data System (ADS)

Sun, Qingshan; Song, Yingli; Liu, Shengnan; Wang, Fei; Zhang, Lin; Xi, Shuhua; Sun, Guifan

2015-10-01

The investigation was carried out to evaluate arsenic exposure and the urine metabolite profiles of workers with different working departments, including administration (Group1), copper ore mining (Group2), copper ore grinding (Group3), electrolytic procession (Group4) and copper smelting (Group5) in a Copper mining and processing plant in China. Information about characteristics of each subject was obtained by questionnaire and inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were determined. The highest urinary levels of iAs, MMA and DMA all were found in the Group 5. Group 4 workers had a higher iAs% and a lower PMI compared to Group 3. The urinary total As (TAs) levels of 54.7% subjects exceeded 50 μg/g Cr, and the highest percentage (93.3%) was found in Group 5, smelters. The results of the present study indicate that workers in copper production plant indeed exposed to As, especially for smelters and workers of electrolytic process.

[Copper nanoparticles as modulators of apoptosis and structural changes in some organs].

PubMed

Sizova, E A; Miroshnikov, S A; Poliakova, V S; Lebedev, S V; Glushchenko, N N

2013-01-01

The effect of repeated intramuscular injection into the organism of copper nanoparticles (CNP) with the diameter of 103 nm on the index of cell readiness to apoptosis and the structure of liver, spleen, kidney, as well as sensomotor cerebral cortex, was studied in 78 male Wistar rats. CNP were injected once per week for 12 weeks. The organs were studied using histological, immunohistochemical and morphometric methods. It was found that after the injections, CNP were distributed into organs and tissues of animals causing structural changes that were specific for eaach tissue. Toxicity of CNP in respect to microgliocytes was demonstrated at a dose of 2 mg/kg, hepatotoxicity and nephrotoxicity--at 6 mg/kg. The increase of CNP load on the organism up to toxic threshold (maximum tolerated dose) resulted in the appearance of signs of dystrophy and tissue necrosis. The data obtained suggest the application of an index of cell readiness to apoptosis, as assessed by caspase 3 expression, as a criterion for evaluation of CNP injection safety.

Wilson disease - currently used anticopper therapy.

PubMed

Członkowska, Anna; Litwin, Tomasz

2017-01-01

Wilson disease (WD) is a genetic disorder of copper metabolism that can be treated successfully with pharmacologic treatment. Two groups of drugs are currently used: chelators (e.g., d-penicillamine and trientine), which increase urinary copper excretion, and zinc salts, which inhibit copper absorption in the digestive tract. The mechanisms of action lead to a negative copper balance, stopping pathologic accumulation of copper in the tissues and clearing affected organs of copper overload. Due to a lack of prospective clinical trials, the use of drugs depends mainly on center experience and the accessibility in different countries or regions. This chapter presents the different reports and recommendations regarding WD treatment. In addition to the different expert opinions on pharmacologic agents, there are a few axioms regarding WD treatment: treatment should start immediately after diagnosis, even in clinically presymptomatic cases; the patient should be treated for life, making compliance a key factor in treatment success; and the treatment should be monitored regularly via liver and hematologic tests, neurologic examination, and copper metabolism, modifying the treatment accordingly. Other drugs proposed for WD treatment (e.g., tetrathiomolybdate) are in clinical trials and lack current recommendations. Thus, only the currently available options for WD pharmacologic treatment are discussed. © 2017 Elsevier B.V. All rights reserved.

[Structure-functional organization of eukaryotic high-affinity copper importer CTR1 determines its ability to transport copper, silver and cisplatin].

PubMed

Skvortsov, A N; Zatulovskiĭ, E A; Puchkova, L V

2012-01-01

It was shown recently, that high affinity Cu(I) importer eukaryotic protein CTR1 can also transport in vitro abiogenic Ag(I) ions and anticancer drug cisplatin. At present there is no rational explanation how CTR1 can transfer platinum group, which is different by coordination properties from highly similar Cu(I) and Ag(I). To understand this phenomenon we analyzed 25 sequences of chordate CTR1 proteins, and found out conserved patterns of organization of N-terminal extracellular part of CTR1 which correspond to initial metal binding. Extracellular copper-binding motifs were qualified by their coordination properties. It was shown that relative position of Met- and His-rich copper-binding motifs in CTR1 predisposes the extracellular CTR1 part to binding of copper, silver and cisplatin. Relation between tissue-specific expression of CTR1 gene, steady-state copper concentration, and silver and platinum accumulation in organs of mice in vivo was analyzed. Significant positive but incomplete correlation exists between these variables. Basing on structural and functional peculiarities of N-terminal part of CTR1 a hypothesis of coupled transport of copper and cisplatin has been suggested, which avoids the disagreement between CTR1-mediated cisplatin transport in vitro, and irreversible binding of platinum to Met-rich peptides.

Copper chelators: chemical properties and bio-medical applications.

PubMed

Tegoni, M; Valensin, D; Toso, L; Remelli, M

2014-01-01

Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.

ATP7B mediates vesicular sequestration of copper: insight into biliary copper excretion.

PubMed

Cater, Michael A; La Fontaine, Sharon; Shield, Kristy; Deal, Yolanda; Mercer, Julian F B

2006-02-01

The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile. It is not clear whether ATP7B translocates excess intrahepatic copper directly across the canalicular membrane or sequesters this copper into exocytic vesicles, which subsequently fuse with canalicular membrane to expel their contents into bile. The aim of this study was to clarify the mechanism underlying ATP7B-mediated copper detoxification by investigating endogenous ATP7B localization in the HepG2 hepatoma cell line and its ability to mediate vesicular sequestration of excess intracellular copper. Immunofluorescence microscopy was used to investigate the effect of copper concentration on the localization of endogenous ATP7B in HepG2 cells. Copper accumulation studies to determine whether ATP7B can mediate vesicular sequestration of excess intracellular copper were performed using Chinese hamster ovary cells that exogenously expressed wild-type and mutant ATP7B proteins. In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported. Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. Expression of wild-type and mutant ATP7B caused Chinese hamster ovary cells to accumulate copper in vesicles, which subsequently undergo exocytosis, releasing copper across the plasma membrane. This report provides compelling evidence that the primary mechanism of biliary copper excretion involves ATP7B-mediated vesicular sequestration of copper rather than direct copper translocation across the canalicular membrane.

40 CFR 141.80 - General requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Control of Lead and Copper § 141.80 General requirements. (a... drinking water regulations for lead and copper. Unless otherwise indicated, each of the provisions of this... and copper action levels measured in samples collected at consumers' taps. (c) Lead and copper action...

Evaluation of Serum Levels of Zinc, Copper, Iron, and Zinc/Copper Ratio in Cutaneous Leishmaniasis

PubMed Central

Pourfallah, F; Javadian, S; Zamani, Z; Saghiri, R; Sadeghi, S; Zarea, B; Faiaz, Sh; Mirkhani, F; Fatemi, N

2009-01-01

Background: The purpose of this study was to evaluate the levels of zinc (Zn), copper (Cu), iron (Fe) and zinc/ copper ratio in the serum of patients with cutaneous leishmaniasis in Qom Province, center of Iran. Methods: Serum levels of zinc and copper were determined by flame atomic absorption spectrophotometer and serum iron concentration was measured by using an Auto Analyzer. The study group consisted of 60 patients with cutaneous leishmaniasis and the control group of 100 healthy volunteers from the same area who were not exposed to cutaneous leishmaniasis. Result: There were no statistically significant differences in age and body mass index between the two groups. Serum Zn (P< 0.001) and Fe (P< 0.05) levels were lower in patients with cutaneous leishmaniasis than the control group. We also found serum Cu concentration (P< 0.05) in the patient group was significantly higher than that of the control group. However, zinc/ copper ratio (P< 0.001) was lower in patients with cutaneous leishmaniasis than in the control group. Conclusion: Our data indicated that Zn/Cu ratio was significantly lower in patients with CL as compared to the controls. Earlier reports suggest that, this ratio imbalance could be a useful marker for immune dysfunction in leishmaniasis. There was also strong association of Zn, Cu and Fe with CL. It suggests the use of blood zinc, copper, iron concentration and the copper/zinc ratio (Zn/Cu), as a means for estimating the prognosis of CL. PMID:22808376

The effect of gastrointestinal parasitism on blood copper and hemoglobin levels in sheep

PubMed Central

2005-01-01

Abstract Endoparasitism is a problem in Trinidad, as it is in most tropical countries. Parasite infection has been suspected to contribute to the pathogenesis of swayback disease (which is also prevalent in Trinidad), but the mode of action has not been clearly defined, although it has been suggested that parasites interfere with the absorption of copper from the gastrointestinal tract. The objectives of the study were to assess the effect of endoparasitism on blood copper levels and hemoglobin (Hb) concentration in sheep in Trinidad. Copper was administered intramuscularly to parasite infected and noninfected animals. The results showed that parasitism has a depressing effect on blood copper and Hb levels, even when administered parenterally. It is concluded that parasitism can aggravate existing hypocupremia and possibly influence the expression of swayback disease. PMID:16363328

The Effect of Helicobacter pylori Eradication on the Levels of Essential Trace Elements

PubMed Central

Wu, Meng-Chieh; Huang, Chun-Yi; Kuo, Fu-Chen; Hsu, Wen-Hung; Wang, Sophie S. W.; Shih, Hsiang-Yao; Liu, Chung-Jung; Chen, Yen-Hsu; Wu, Deng-Chyang; Huang, Yeou-Lih; Lu, Chien-Yu

2014-01-01

Objective. This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. Patients and Methods. We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. Results. Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. Conclusion. H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327). PMID:25548772

Spatial investigation of the elemental distribution in Wilson's disease liver after d-penicillamine treatment by LA-ICP-MS.

PubMed

Hachmöller, Oliver; Zibert, Andree; Zischka, Hans; Sperling, Michael; Groba, Sara Reinartz; Grünewald, Inga; Wardelmann, Eva; Schmidt, Hartmut H-J; Karst, Uwe

2017-12-01

At present, the copper chelator d-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10μm) laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method was applied. Untreated LPP -/- rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA-ICP-MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Accuracy of the radioactive copper incorporation test in the diagnosis of Wilson disease.

PubMed

Członkowska, Anna; Rodo, Maria; Wierzchowska-Ciok, Agata; Smolinski, Lukasz; Litwin, Tomasz

2018-02-08

In Wilson disease (WD), copper accumulates in the liver and other tissues because of mutations in the ATP7B copper transporter gene. Early and effective anticopper treatment is crucial. However, routine diagnostic methods based on clinical findings, copper metabolism tests, liver biopsies and DNA analyses do not always provide a conclusive diagnosis. The aim was to evaluate radioactive copper incorporation as a diagnostic test. We included cases with a diagnosis of WD supported by radiocopper testing and later, when available, confirmed by DNA analysis. Incorporation of 64 Cu was measured at 2, 24 and 48 hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [AUC]), sensitivity, specificity and predictive value were assessed for 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios and compared with serum measurements of ceruloplasmin, copper, non-ceruloplasmin-bound copper and urinary 24-hours copper excretion. Patients having two pathogenic ATP7B mutations (homozygotes/compound heterozygotes) (n = 74) had significantly lower 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios than heterozygote controls (n = 21) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both P < .001). Of note, 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios had excellent diagnostic accuracy, with AUCs approaching 1, and only 24-hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity. The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP7B function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-hepatic tumors change the activity of genes encoding copper trafficking proteins in the liver

PubMed Central

Babich, Polina S.; Skvortsov, Alexey N; Rusconi, Paolo; Tsymbalenko, Nadezhda V.; Mutanen, Marja; Puchkova, Ludmila V.; Broggini, Massimo

2013-01-01

To assess the statistical relationship between tumor growth and copper metabolism, we performed a metaanalysis of studies in which patients with neoplasms were characterized according to any of the copper status indexes (atomic copper serum concentration, serum oxidase activity, ceruloplasmin protein content). Our metaanalysis shows that in the majority of cases (more than 3100 patients), tumor growth positively correlates with the copper status indexes. Nude athymic CD-1 nu/nu mice with subcutaneous tumors of human origin, C57Bl/6J mice with murine melanoma and ApcMin mice with spontaneously developing adenomas throughout the intestinal tract were studied to experimentally determine the relationship between tumor progression, liver copper metabolism, and copper status indexes. We showed that the copper status indexes increased significantly during tumor growth. In the liver tissue of tumor-bearing mice, ceruloplasmin gene expression, as well as the expression of genes related to ceruloplasmin metallation (CTR1 and ATP7B), increased significantly. Moreover, the presence of an mRNA splice variant encoding a form of ceruloplasmin anchored to the plasma membrane by glycosylphosphatidyl inositol, which is atypical for hepatocytes, was also detected. The ATP7A copper transporter gene, which is normally expressed in the liver only during embryonic copper metabolism, was also activated. Depletion of holo-ceruloplasmin resulted in retardation of human HCT116 colon carcinoma cell growth in nude mice and induced DNA fragmentation in tumor cells. In addition, the concentration of cytochrome c increased significantly in the cytosol, while decreasing in the mitochondria. We discuss a possible trans-effect of developing tumors on copper metabolism in the liver. PMID:23792645

Heavy metal pollution among autoworkers. II. Cadmium, chromium, copper, manganese, and nickel.

PubMed Central

Clausen, J; Rastogi, S C

1977-01-01

Garages and auto-repair workshops may be polluted with other heavy metals besides lead. Blood of autoworkers with high lead content was analysed for cadmium, chromium, copper manganese, nickel, ALAD activity and carboxyhaemoglobin level. Cadmium and copper levels in blood of autoworkers were comparable with those of the control subjects while chroimium and nickel levels were significantly higher (P less than 0-01 for both metals), and scattered raised values of manganese were found. There was no significant mutual correlation between levels of various heavy metals determined in whole blood. High copper levels were slightly related to decreasing ALAD activity (P less than 0-1). Nineteen per cent of autoworkers were found to have an abnormally blood level of carboxyhaemoglobin. The amount of particulate heavy metal in autoworkshop air was not related to biochemical abnormalities found in the autoworkers. Various sources of pollution of these heavy metals in autoworkshops are discussed. PMID:71915

Factors controlling peat chemistry and vegetation composition in Sudbury peatlands after 30 years of pollution emission reductions.

PubMed

Barrett, Sophie E; Watmough, Shaun A

2015-11-01

The objective of this research was to assess factors controlling peat and plant chemistry, and vegetation composition in 18 peatlands surrounding Sudbury after more than 30 years of large (>95%) pollution emission reductions. Sites closer to the main Copper Cliff smelter had more humified peat and the surface horizons were greatly enriched in copper (Cu) and nickel (Ni). Copper and Ni concentrations in peat were significantly correlated with that in the plant tissue of Chamaedaphne calyculata. The pH of peat was the strongest determining factor for species richness, diversity, and community composition, although percent vascular plant cover was strongly negatively correlated with surface Cu and Ni concentrations in peat. Sphagnum frequency was also negatively related to peat Cu and Ni concentrations indicating sites close to Copper Cliff smelter remain adversely impacted by industrial activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Copper and Lead Corrosion in a Full Scale Home Plumbning system Simulation

EPA Science Inventory

The corrosion of household or premise plumbing materials (such as copper, brass, and solder) and the metal release that results from that corrosion can cause numerous problems, ranging from elevated lead and copper levels to blue water and copper pinhole leaks. If left untreate...

Aquatic Life Criteria - Copper

EPA Pesticide Factsheets

Documents pertain to Aquatic Life Ambient Water Quality criteria for Copper (2007 Freshwater, 2016 Estuarine/marine). These documents contain the safe levels of Copper in water that should protect to the majority of species.

Molecular characterization of a cDNA encoding copper/zinc superoxide dismutase from cultured cells of Manihot esculenta.

PubMed

Shin, Seung-Yong; Lee, Haeng-Soon; Kwon, Suk-Yoon; Kwon, Soon-Tae; Kwak, Sang-Soo

2005-01-01

Superoxide dismutase (SOD) cDNA, mSOD2, encoding cytosolic copper/zinc SOD (CuZnSOD) cDNA was isolated from suspension-cultured cells of cassava (Manihot esculenta Crantz) by cDNA library screening, and its expression was investigated in relation to environmental stress. mSOD2 is 774 bp in length with an open reading frame (ORF) of 152 amino acids, corresponding to a protein of predicted molecular mass 15 kDa and a pI of 5.22. One copy of the mSOD2 gene was found to be present in the cassava genome by Southern analysis using an mSOD2 cDNA-specific probe. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed diverse expression patterns for the mSOD2 gene in various tissues of intact cassava plants, at various stages of the growth in suspension cultures, and in the leaf tissues exposed to different stresses. The mSOD2 gene was highly expressed in suspension-cultured cells and in the stems of intact plants. However, it was expressed at low levels in leaves and roots. During suspension cell growth, the mSOD2 transcript progressively increased during culture. Moreover, the mSOD2 gene in excised cassava leaves responded to various stresses in different ways. In particular, it was highly induced in leaf tissue by several abiotic stresses, including high temperature (37 degrees C), chilling (4 degrees C), methyl viologen (MV) exposure, and wounding treatment. These results indicate that the mSOD2 gene is involved in the antioxidative process triggered by oxidative stress induced by environmental change.

Acute gastrointestinal effects of graded levels of copper in drinking water.

PubMed Central

Pizarro, F; Olivares, M; Uauy, R; Contreras, P; Rebelo, A; Gidi, V

1999-01-01

The objective of this study was to determine the acute gastrointestinal effects caused by the consumption of drinking water containing graded levels of added copper. Sixty healthy, adult women were randomly assigned to receive copper [Cu(II)] at four concentrations in their drinking water following a Latin-square design. Each group (n = 15) received tap water with no added copper, 1, 3, and 5 mg Cu/l of added copper sulfate for a 2-week study period, followed by 1 week of standard tap water. The subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. The average daily consumption of water was 1.64 liters per subject, regardless of the amount of copper added. Final serum copper, ceruloplasmin, and liver enzymes were measured in all subjects and were not different from baseline concentrations. Twenty-one subjects (35%) recorded gastrointestinal disturbances sometime during the study, 9 had diarrhea, some with abdominal pain and vomiting, and 12 subjects presented abdominal pain, nausea, or vomiting. There was no association between copper levels in drinking water and diarrhea. However, nausea, abdominal pain, or vomiting were significantly related to copper concentrations in water. The recorded incidence rate of these symptoms was 5, 2, 17, and 15% while ingesting water with 0, 1, 3, and 5 mg Cu/l, respectively (overall [chi]2 = 11.3, p<0.01; Cu [less than/equal to]1 mg/l versus Cu [Greater than/equal to]3 mg/l, [chi]2, p<0.01). When subjects interrupted their consumption of drinking water with added copper, most symptoms disappeared. We conclude that under the conditions of the study, there was no association between aggregate copper in drinking water within the range of 0-5 mg/l and diarrhea, but a [Greater than/equal to]3 mg Cu/l level of ionized copper was associated with nausea, abdominal pain, or vomiting. Additional studies with sufficient numbers of subjects are needed to define thresholds for specific gastrointestinal symptoms with precision and to extrapolate these results to the population at large. Images Figure 1 Figure 2 PMID:9924006

Occurrence of the Transferable Copper Resistance Gene tcrB among Fecal Enterococci of U.S. Feedlot Cattle Fed Copper-Supplemented Diets

PubMed Central

Amachawadi, R. G.; Alvarado, C. A.; Mainini, T. R.; Vinasco, J.; Drouillard, J. S.; Nagaraja, T. G.

2013-01-01

Copper, an essential micronutrient, is supplemented in the diet at elevated levels to reduce morbidity and mortality and to promote growth in feedlot cattle. Gut bacteria exposed to copper can acquire resistance, which among enterococci is conferred by a transferable copper resistance gene (tcrB) borne on a plasmid. The present study was undertaken to investigate whether the feeding of copper at levels sufficient to promote growth increases the prevalence of the tcrB gene among the fecal enterococci of feedlot cattle. The study was performed with 261 crossbred yearling heifers housed in 24 pens, with pens assigned randomly to a 2×2 factorial arrangement of treatments consisting of dietary copper and a commercial linseed meal-based energy protein supplement. A total of 22 isolates, each identified as Enterococcus faecium, were positive for tcrB with an overall prevalence of 3.8% (22/576). The prevalence was higher among the cattle fed diets supplemented with copper (6.9%) compared to normal copper levels (0.7%). The tcrB-positive isolates always contained both erm(B) and tet(M) genes. Median copper MICs for tcrB-positive and tcrB-negative enterococci were 22 and 4 mM, respectively. The transferability of the tcrB gene was demonstrated via a filter-mating assay. Multilocus variable number tandem repeat analysis revealed a genetically diverse population of enterococci. The finding of a strong association between the copper resistance gene and other antibiotic (tetracycline and tylosin) resistance determinants is significant because enterococci remain potential pathogens and have the propensity to transfer resistance genes to other bacteria in the gut. PMID:23666328

Copper-complexing ligands produced by an intact estuarine microbial community in response to copper stress.

NASA Astrophysics Data System (ADS)

Bingham, J.; Dryden, C.; Gordon, A.

2002-12-01

Copper is both an important nutrient and a pollutant in the marine environment. By studying the interactions between microorganisms and copper in the Elizabeth River (VA), home to a major Naval Base, we field tested the hypothesis that picoplankton and/or bacterioplankton produce strong, copper-complexing ligands in response to elevated copper concentrations. A simple light/ dark test was used to distinguish between heterotrophic and phototrophic ligand production. Samples were bottled and moored, submerged one meter, for a week. Direct counts using DAPI stain and epiflourescence were conducted to find concentrations of picoplankton and bacterioplankton. Using cathodic stripping voltammetry, we found the total copper concentrations, and then from a titration of the ligands by copper, the ligand concentrations and conditional stability constants were obtained. The Elizabeth River naturally had between 10-20 nM total dissolved copper concentrations. However when copper complexation was considered we found that the levels of bio-available Cu(II) ions were much lower. In fact in the natural samples the levels were not high enough to affect the relative reproductive rates of several microorganisms. Naturally there was a 50 nM "buffer zone" of ligand to total dissolved copper concentration. Furthermore, when stressed with excess copper, healthy picoplankton produced enough ligand to alleviate toxicity, and rebuild the buffer zone. However bacterioplankton only produced enough ligand so that they were no longer affected. Therefore, intact estuarine communities regulate copper bioavailability and toxicity with ligand production.

Copper ions stimulate the proliferation of hepatic stellate cells via oxygen stress in vitro.

PubMed

Xu, San-qing; Zhu, Hui-yun; Lin, Jian-guo; Su, Tang-feng; Liu, Yan; Luo, Xiao-ping

2013-02-01

This study examined the effect of copper ions on the proliferation of hepatic stellate cells (HSCs) and the role of oxidative stress in this process in order to gain insight into the mechanism of hepatic fibrosis in Wilson's disease. LX-2 cells, a cell line of human HSCs, were cultured in vitro and treated with different agents including copper sulfate, N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO) for different time. The proliferation of LX-2 cells was measured by non-radioactive cell proliferation assay. Real-time PCR and Western blotting were used to detect the mRNA and protein expression of platelet-derived growth factor receptor β subunit (PDGFβR), ELISA to determine the level of glutathione (GSH) and oxidized glutathione (GSSG), dichlorofluorescein assay to measure the level of reactive oxygen species (ROS), and lipid hydroperoxide assay to quantify the level of lipid peroxide (LPO). The results showed that copper sulfate over a certain concentration range could promote the proliferation of LX-2 cells in a time- and dose-dependent manner. The effect was most manifest when LX-2 cells were treated with copper sulfate at a concentration of 100 μmol/L for 24 h. Additionally, copper sulfate could dose-dependently increase the levels of ROS and LPO, and decrease the ratio of GSH/GSSG in LX-2 cells. The copper-induced increase in mRNA and protein expression of PDGFβR was significantly inhibited in LX-2 cells pre-treated with NAC, a precursor of GSH, and this phenomenon could be reversed by the intervention of BSO, an inhibitor of NAC. It was concluded that copper ions may directly stimulate the proliferation of HSCs via oxidative stress. Anti-oxidative stress therapies may help suppress the copper-induced activation and proliferation of HSCs.

The influence of duckweed species diversity on ecophysiological tolerance to copper exposure.

PubMed

Zhao, Zhao; Shi, Huijuan; Duan, Dongzhu; Li, Hongmei; Lei, Tingwen; Wang, Maolin; Zhao, Hai; Zhao, Yun

2015-07-01

In excess, copper is toxic to plants. In the plants, Landoltia punctata and Lemna minor grown in mixed and monoculture, the effects of exposure to varying concentrations of copper (0.01, 0.1, 0.5 and 1mgL(-1) Cu) for seven days were assessed by measuring changes in the chlorophyll, protein and malondialdehyde (MDA) content, catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX) activity. According to results, Cu levels in plants increased with increasing Cu concentration. The level of photosynthetic pigments and crude proteins decreased only upon exposure to high Cu concentrations. However, the starch and malondialdehyde (MDA) content increased. These results suggested a stress alleviation that was possibly the result of antioxidants such as CAT and SOD, the activities of which increased with increasing Cu levels. APX activity increased in L. punctata, but decreased in L. minor, under monoculture or mixed culture conditions. In addition, the duckweed in mixed culture exhibited increased antioxidant enzyme activities which provide increased resistance to copper in moderate copper concentrations. As the copper concentration increased, the duckweed in the mixed culture limited the uptake of copper to avoid toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Observations on the preparation of sections of dental hard and soft tissues without conventional embedding procedures.

PubMed

Mok, Y C; Fearnhead, R W

1985-09-01

Inexpensive thin copper discs loaded with diamonds embedded in small slits around the periphery, may be used to cut sections from unembedded tooth samples without disrupting the cellular and extracellular components intimately associated with hard tissue interfaces. The tissue may be unfixed, fixed or cut using fixation or dye solutions as the lubricant. The use of these discs therefore opens up new avenues of histochemical investigation of hard tissue unrestricted by those artefacts associated with conventional or traditional methods of preparation.

Decreased erythrocyte CCS content is a biomarker of copper overload in rats.

PubMed

Bertinato, Jesse; Sherrard, Lindsey; Plouffe, Louise J

2010-07-02

Copper (Cu) is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS content in erythrocytes is particularly sensitive to decreased Cu status. Given the lack of a non-invasive, sensitive and specific biomarker for the assessment of Cu excess, we investigated whether CCS expression in erythrocytes reflects Cu overload. Rats were fed diets containing normal or high levels of Cu for 13 weeks. Diets contained 6.3 +/- 0.6 (Cu-N), 985 +/- 14 (Cu-1000) or 1944 +/- 19 (Cu-2000) mg Cu/kg diet. Rats showed a variable response to the high Cu diets. Some rats showed severe Cu toxicity, while other rats showed no visible signs of toxicity and grew normally. Also, some rats had high levels of Cu in liver, whereas others had liver Cu concentrations within the normal range. Erythrocyte CCS protein expression was 30% lower in Cu-2000 rats compared to Cu-N rats (P < 0.05). Notably, only rats that accumulated high levels of Cu in liver had lower erythrocyte CCS (47% reduction, P < 0.05) compared to rats fed normal levels of Cu. Together, these data indicate that decreased erythrocyte CCS content is associated with Cu overload in rats and should be evaluated further as a potential biomarker for assessing Cu excess in humans.

PIXE analysis of mineral matter in thin sections of human lung

NASA Astrophysics Data System (ADS)

Annegarn, H. J.; Pillay, A. E.; Da Vies, J. C. A.; Faure, D.; Sellschop, J. P. F.

1988-12-01

It is postulated that insoluble mineral residues in the lungs of deceased miners may provide a quantitative measure of the integrated lifetime dust exposure. For epidemiological surveys rapid instrumental techniques are required to analyse representative samples of lung tissue. Particle-induced X-ray emission (PIXE) has been evaluated for analysis of microtomed slices of wax-embedded lung and lymph node (Hilar gland) tissue from deceased miners. The 50 μm slices, mounted on Mylar backings and placed in a He atmosphere, were irradiated using 3.2 MeV protons. PIXE analysis provided adequate sensitivity for key mineral elements including Si, Cr and Ti. The porous, nonuniform nature of lung tissue made it impossible to measure the tissue mass in the irradiated area, preventing the calculation of mass concentrations. Instead, biological sulphur was used as an internal standard, assuming that the fraction of S in soft, fat-free tissue is constant. Results are presented for lung and lymph node tissue from gold, chrome, copper, platinum and asbestos miners. Si mineral residues in lymph node tissue were found to be concentrated by a factor 50 relative to lung. Cr residues were clearly observed in the chrome miner's lung, but no excess of Cu was present in the copper miner's lung. There is evidence of preferential Si removal relative to Ti. Results warrant further development of PIXE for scanning of large numbers of lung samples prepared in the above manner.

Trace metal depositional patterns from an open pit mining activity as revealed by archived avian gizzard contents.

PubMed

Bendell, L I

2011-02-15

Archived samples of blue grouse (Dendragapus obscurus) gizzard contents, inclusive of grit, collected yearly between 1959 and 1970 were analyzed for cadmium, lead, zinc, and copper content. Approximately halfway through the 12-year sampling period, an open-pit copper mine began activities, then ceased operations 2 years later. Thus the archived samples provided a unique opportunity to determine if avian gizzard contents, inclusive of grit, could reveal patterns in the anthropogenic deposition of trace metals associated with mining activities. Gizzard concentrations of cadmium and copper strongly coincided with the onset of opening and the closing of the pit mining activity. Gizzard zinc and lead demonstrated significant among year variation; however, maximum concentrations did not correlate to mining activity. The archived gizzard contents did provide a useful tool for documenting trends in metal depositional patterns related to an anthropogenic activity. Further, blue grouse ingesting grit particles during the time of active mining activity would have been exposed to toxicologically significant levels of cadmium. Gizzard lead concentrations were also of toxicological significance but not related to mining activity. This type of "pulse" toxic metal exposure as a consequence of open-pit mining activity would not necessarily have been revealed through a "snap-shot" of soil, plant or avian tissue trace metal analysis post-mining activity. Copyright © 2010 Elsevier B.V. All rights reserved.

7 CFR 1755.200 - RUS standard for splicing copper and fiber optic cables.

Code of Federal Regulations, 2011 CFR

2011-01-01

... making an OTDR test at the same time a splice is being fused. (7) Cable preparation. (i) Engineering work.... Reagent grade isopropyl alcohol is a commonly used cleaning solvent. (ii) A tissue or cotton ball shall be... using a clean tissue or cotton ball for each coated fiber. Caution shall be exercised to avoid removing...

The influence of long-term copper contaminated agricultural soil at different pH levels on microbial communities and springtail transcriptional regulation.

PubMed

de Boer, Tjalf E; Taş, Neslihan; Braster, Martin; Temminghoff, Erwin J M; Röling, Wilfred F M; Roelofs, Dick

2012-01-03

Copper has long been applied for agricultural practises. Like other metals, copper is highly persistent in the environment and biologically active long after its use has ceased. Here we present a unique study on the long-term effects (27 years) of copper and pH on soil microbial communities and on the springtail Folsomia candida an important representative of the soil macrofauna, in an experiment with a full factorial, random block design. Bacterial communities were mostly affected by pH. These effects were prominent in Acidobacteria, while Actinobacteria and Gammaroteobacteria communities were affected by original and bioavailable copper. Reproduction and survival of the collembolan F. candida was not affected by the studied copper concentrations. However, the transcriptomic responses to copper reflected a mechanism of copper transport and detoxification, while pH exerted effects on nucleotide and protein metabolism and (acute) inflammatory response. We conclude that microbial community structure reflected the history of copper contamination, while gene expression analysis of F. candida is associated with the current level of bioavailable copper. The study is a first step in the development of a molecular strategy aiming at a more comprehensive assessment of various aspects of soil quality and ecotoxicology.

Effects of Water Quality and Orthophosphate on Surface Characteristics of Cu Corrosion in Drinking Water using Atomic Force Microscopy

EPA Science Inventory

Since the passage of the Lead and Copper Rule (LCR) in 1991, researchers have examined the effects of water chemistry on the solubility of copper to establish best approaches for reducing copper levels. Despite recent developments, important gaps still exist regarding copper cor...

Insights into the mechanism of copper-tolerance in Fibroporia radiculosa: The biosynthesis of oxalate

Treesearch

Katie Jenkins; Carol A. Clausen; Frederick Green; Susan V. Diehl

2015-01-01

Copper is currently used as the key component in wood preservatives despite the known tolerance of many brown-rot Basidiomycetes. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate when exposed to copper. To gain insight into the mechanism of oxalate production, four F. radiculosa...

Circulation of copper in the biotic compartments of a freshwater dammed reservoir.

PubMed

Vinot, I; Pihan, J C

2005-01-01

This study concerns a chronic copper release in an aquatic ecosystem: Mirgenbach reservoir; which is characterized by high salinity, conductivity and hardness, a eutrophic state and a high temperature. To study the bioavailability of copper in the biotic compartments, the sampling covered the entire food chain (phyto- and zooplankton, macroalgae, aquatic plants, crustaceans, mollusks, and fish). Of the organisms present, the filter feeder Dreissena polymorpha, the detritivorous Bithynia tentaculata and Orconectes limosus were most contaminated by copper. The level of copper found in fish was the lowest. Body copper concentrations recorded in the present study show large variability between species even in some that are closely related. In most cases, however, the metal handling strategy, feeding habits, morphology and ecology can, at least partially, explain the metal content recorded. Pollution factors have been used to assess the state of contamination of the food chain. This study showed finally that the copper in the lake is bioavailable and bioaccumulated by organisms up to high levels and some effects of long-term toxicity of copper on benthic community and planktonic biomass were pointed out.

Enzymatic mechanism of oxalate production in the TCA and glyoxylate pathways using various isolates of Antrodia radiculosa

Treesearch

K.M. Jenkins; S.V. Diehl; C.A. Clausen; F. Green

2011-01-01

Brown-rot fungi produce oxalate in large amounts; however, levels of accumulation and function vary by species. Copper-tolerant fungi, like Antrodia radiculosa, produce and accumulate high levels of oxalate in response to copper. Oxalate biosynthesis in copper-tolerant fungi has been linked to the glyoxylate and tricarboxylic acid (TCA) cycles. Within these two cycles...

Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae.

PubMed

Watanabe, Daisuke; Kikushima, Rie; Aitoku, Miho; Nishimura, Akira; Ohtsu, Iwao; Nasuno, Ryo; Takagi, Hiroshi

2014-07-07

The basic amino acid histidine inhibited yeast cell growth more severely than lysine and arginine. Overexpression of CTR1 , which encodes a high-affinity copper transporter on the plasma membrane, or addition of copper to the medium alleviated this cytotoxicity. However, the intracellular level of copper ions was not decreased in the presence of excess histidine. These results indicate that histidine cytotoxicity is associated with low copper availability inside cells, not with impaired copper uptake. Furthermore, histidine did not affect cell growth under limited respiration conditions, suggesting that histidine cytotoxicity is involved in deficiency of mitochondrial copper.

Copper activation of organophosporus compounds detoxication by chicken serum.

PubMed

Monroy-Noyola, Antonio; Sogorb, Miguel Angel; Díaz-Alejo, Nuria; Vilanova, Eugenio

2017-08-01

Avian species contain low levels of enzymes that hydrolyze organophosphorus compounds (OPs), and chickens are used as a model of OPs delayed neurotoxicity. For both reasons, we studied the ability of chicken tissue for OP detoxication. A significant activating effect of Cu 2+ on the hydrolysis of O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) was observed in hen plasma and the microsomal fractions of the liver, brain, and mainly in hen serum, by spectrophotometric and chiral chromatography methods. The concentration of 1 mM of Cu 2+ or Zn 2+ showed 200% and 168% activation, respectively, in hen plasma compared with the Ca 2+ -dependent hydrolysis, whereas these cations had an inhibitory effect on soluble liver and brain fractions. An increase of 1.5 to 19.5 fold in HDCP hydrolyzing activity was obtained for the 30-250 μM Cu 2+ range when using chicken serum instead of hen plasma. This Cu 2+ -dependent hydrolysis in chicken serum was stereoselective for the R-(+)-HDCP isomer, which proved the opposite to the Ca 2+ -dependent stereoselective hydrolysis of the S-(-)-HDCP isomer reported in rat and rabbit serum. The level of copper needed to exert this effect should be further evaluated for its suitability for potential therapeutic and biotechnological applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of an Extract from Aronia melanocarpa L. Berries on the Body Status of Zinc and Copper under Chronic Exposure to Cadmium: An In Vivo Experimental Study.

PubMed

Borowska, Sylwia; Brzóska, Małgorzata M; Gałażyn-Sidorczuk, Małgorzata; Rogalska, Joanna

2017-12-19

In an experimental model of low-level and moderate environmental human exposure to cadmium (Cd), it was investigated whether the consumption of a polyphenol-rich Aronia melanocarpa L. berries (chokeberries) extract (AE) may influence the body status of zinc (Zn) and copper (Cu). The bioelements' apparent absorption, body retention, serum and tissue concentrations, total pool in internal organs, excretion, and the degree of binding to metallothionein were evaluated in female rats administered 0.1% aqueous AE or/and Cd in their diet (1 and 5 mg/kg) for 3-24 months. The consumption of AE alone had no influence on the body status of Zn and Cu. The extract administration at both levels of Cd treatment significantly (completely or partially) protected against most of the changes in the metabolism of Zn and Cu caused by this xenobiotic; however, it increased or decreased some of the Cd-unchanged indices of their body status. Based on the findings, it seems that rational amounts of chokeberry products may be included in the daily diet without the risk of destroying Zn and Cu metabolisms; however, their potential prophylactic use under exposure to Cd needs further study to exclude any unfavourable impact of these essential elements on the metabolism.

2016 Draft Estuarine/Marine Copper Aquatic Life Ambient Water Quality Criteria

EPA Pesticide Factsheets

Documents pertain to Aquatic Life Ambient Water Quality criteria for Copper (2016 Estuarine/marine). These documents contain the safe levels of Copper in water that should protect to the majority of species.

Copper in the sediment and sea surface microlayer near a fallowed, open-net fish farm.

PubMed

Loucks, Ronald H; Smith, Ruth E; Fisher, Clyde V; Fisher, E Brian

2012-09-01

Sediment and sea surface microlayer samples near an open-net salmon farm in Nova Scotia, were analysed for copper. Copper is a constituent of the feed and is an active ingredient of anti-foulants. The salmon farm was placed in fallow after 15 years of production. Sampling was pursued over 27 months. Elevated copper concentrations in the sediments indicated the farm site as a source. Bubble flotation due to gas-emitting sediments from eutrophication is a likely process for accumulating copper in the sea surface microlayer at enriched concentrations. Elevated and enriched concentrations in the sea surface microlayer over distance from the farm site led, as a result of wind-drift, to an enlarged farm footprint. The levels of copper in both sediments and sea surface microlayer exceeded guidelines for protection of marine life. Over the 27 months period, copper levels persisted in the sediments and decreased gradually in the sea surface microlayer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Zinc in denture adhesive: a rare cause of copper deficiency in a patient on home parenteral nutrition

PubMed Central

Prasad, Rakesh; Hawthorne, Barney; Durai, Dharmaraj; McDowell, Ian

2015-01-01

A 65-year-old woman with Crohn's disease, who had been on home parenteral nutrition for many years, presented with perioral paraesthesia and a burning sensation in the mouth. Initial blood tests including serum ferritin, vitamin B12 and folate, were normal apart from mild pancytopaenia. Serum copper was low, in spite of receiving regular copper in her parenteral feeds. The copper in her parenteral feeds was increased initially, but when it did not improve, she was started on weekly intravenous copper infusions. She was using dental adhesive, which had zinc in it, and a possibility that this was causing her copper deficiency was raised. Serum zinc levels were normal, but urinary zinc was very high. The patient was advised to use zinc-free dental adhesive and her copper level returned to normal within a few months with normalisation of her pancytopaenia, and partial resolution of her oral paraesthesia. PMID:26452740

COPT6 Is a Plasma Membrane Transporter That Functions in Copper Homeostasis in Arabidopsis and Is a Novel Target of SQUAMOSA Promoter-binding Protein-like 7*

PubMed Central

Jung, Ha-il; Gayomba, Sheena R.; Rutzke, Michael A.; Craft, Eric; Kochian, Leon V.; Vatamaniuk, Olena K.

2012-01-01

Among the mechanisms controlling copper homeostasis in plants is the regulation of its uptake and tissue partitioning. Here we characterized a newly identified member of the conserved CTR/COPT family of copper transporters in Arabidopsis thaliana, COPT6. We showed that COPT6 resides at the plasma membrane and mediates copper accumulation when expressed in the Saccharomyces cerevisiae copper uptake mutant. Although the primary sequence of COPT6 contains the family conserved domains, including methionine-rich motifs in the extracellular N-terminal domain and a second transmembrane helix (TM2), it is different from the founding family member, S. cerevisiae Ctr1p. This conclusion was based on the finding that although the positionally conserved Met106 residue in the TM2 of COPT6 is functionally essential, the conserved Met27 in the N-terminal domain is not. Structure-function studies revealed that the N-terminal domain is dispensable for COPT6 function in copper-replete conditions but is important under copper-limiting conditions. In addition, COPT6 interacts with itself and with its homolog, COPT1, unlike Ctr1p, which interacts only with itself. Analyses of the expression pattern showed that although COPT6 is expressed in different cell types of different plant organs, the bulk of its expression is located in the vasculature. We also show that COPT6 expression is regulated by copper availability that, in part, is controlled by a master regulator of copper homeostasis, SPL7. Finally, studies using the A. thaliana copt6-1 mutant and plants overexpressing COPT6 revealed its essential role during copper limitation and excess. PMID:22865877

Physiological serum copper concentrations found in malignancies cause unfolding induced aggregation of human serum albumin in vitro.

PubMed

Rizvi, Asim; Furkan, Mohd; Naseem, Imrana

2017-12-15

Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed. Copyright © 2017. Published by Elsevier Inc.

Impact of Plumbing Age on Copper Levels in Drinking Water

EPA Science Inventory

Theory and limited practical experiences suggest that higher copper levels in drinking water tap samples are typically associated with newer plumbing systems, and levels decrease with increasing plumbing age. Past researchers have developed a conceptual model to explain the “agin...

Levels of heavy metals in green-lipped mussel Perna veridis (Linnaeus) from Muar Estuary, Johore, Malaysia.

PubMed

Kamaruzzaman, B Y; Ong, M C; Zaleha, K; Shahbudin, S

2008-09-15

Muscle and feather in tissue of 40 juveniles and 40 adult green-lipped mussel Perna veridis (L.) collected from Muar Estuary, Johor were analyzed for copper (Cu), cadmium (Cd), lead (Pb) and zinc (Zn) concentration using a fast and sensitive Inductively Coupled Plasma Mass Spectrometer (ICP-MS). In this study, the average concentration of Cu was 8.96 microg g(-1) dry weights, Cd with 0.58 microg g(-1) dry weight, Pb averaging 2.28 microg g(-1) dry weights and Zn averaged to 86.73 microg g(-1) dry weight. The highest accumulation of metal studied was found in feather sample compared to the muscle. The positive relationship of Cu, Cd, Pb and Zn with P. virdis length suggesting that the accumulation of these metals were formed in the mussel. In all cases, metal levels found were lower than the guideline of international standards of reference and the examined bivalve were not associated with enhanced metal content in their tissues and were safe within the limits for human consumption.

Regenerative biomaterials that "click": simple, aqueous-based protocols for hydrogel synthesis, surface immobilization, and 3D patterning.

PubMed

Nimmo, Chelsea M; Shoichet, Molly S

2011-11-16

The click chemistry era has generated a library of versatile "spring-loaded" reactions that offer high yields, regio- and stereospecificity, and outstanding functional group tolerance. These powerful transformations are particularly advantageous for the design of sophisticated biomaterials that require high levels of precision and control, namely, materials that promote tissue regeneration such as hydrogels, 2D functionalized substrates, and 3D biomimetic scaffolds. In this review, the synthesis and application of regenerative biomaterials via click chemistry are summarized. Particular emphasis is placed on the copper(I)-catalyzed alkyne-azide cycloaddition, Diels-Alder cycloadditions, and thiol-click coupling.

Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects.

PubMed

De Riccardis, L; Buccolieri, A; Muci, M; Pitotti, E; De Robertis, F; Trianni, G; Manno, D; Maffia, M

2018-05-01

Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of Copper and Hydrogen Peroxide Treatments on the Biology, Biomechanics, and Cytotoxicity of Decellularized Dermal Allografts.

PubMed

Leow-Dyke, Sophie F; Rooney, Paul; Kearney, John N

2016-03-01

Decellularized tissue allografts are paving the way as an alternative to cellular tissue transplantation. Effective sterilization or decontamination of tissue allografts is paramount for the safety of the allograft; however, some of the current sterilization procedures have a detrimental effect on the tissue scaffold. The bactericidal and virucidal activity of copper (II) ions and hydrogen peroxide (H2O2) have been widely reported, however, their effect on the biology, biochemistry, and biocompatibility of decellularized tissue have yet to be elucidated. In this study, decellularized human dermis (dCELL human dermis) was treated with copper (II) chloride (CuCl2) and H2O2; both singly and in combination, and parameters, including concentration, pH, and synergy between CuCl2 and H2O2, were evaluated to identify conditions where any detrimental effects on the tissue scaffold were observed. Skin from 13 human donors was retrieved with appropriate consent and processed into dCELL human dermis. The dCELL human dermis was then treated for 3 h with 0.1 mg/L-1 g/L (w/v) CuCl2 and 0.01-7.5% (v/v) H2O2 and combinations of both of these in the same concentration range. dCELL human dermis treated with solutions of 0.1 mg/L-1 g/L CuCl2 or 0.01-7.5% H2O2 caused no detrimental effects on gross histology, collagen denaturation, collagen orientation, and biomechanical properties of the tissue or cytotoxicity. The highest combined concentration of CuCl2 and H2O2 demonstrated an increase in ultimate tensile strength, loss of collagen type IV immunostaining at the dermal-epidermal junction, and in vitro cytotoxicity. Combinations within the range of up to 10 mg/L CuCl2 with up to 0.5% H2O2 had no effect. The data identify the concentrations of CuCl2 and H2O2 solutions that have no effect on the biological, biomechanical, and biochemical properties of dCELL human dermis, while retaining biocompatibility. These treatments may be suitable for use as sterilization/decontamination agents on human decellularized tissues.

An urgent need to reassess the safe levels of copper in the drinking water: lessons from studies on healthy animals harboring no genetic deficits.

PubMed

Pal, Amit; Jayamani, Jayagandan; Prasad, Rajendra

2014-09-01

Recent seminal studies have established neurodegeneration, cognitive waning and/or β-amyloid deposition due to chronic copper intoxication via drinking water in healthy animals; henceforth, fuelling the debate all again over the safe levels of copper in the drinking water. This review encompasses the contemporary imperative animal studies in which the effect of chronic copper toxicity (especially via drinking water) was evaluated on the central nervous system and memory of uncompromised animals along with discussing the future perspectives. Copyright © 2014 Elsevier Inc. All rights reserved.

Copper toxicity and bioaccumulation in Chinese cabbage (Brassica pekinensis Rupr.).

PubMed

Xiong, Zhi-Ting; Wang, Hai

2005-04-01

Copper is among the major heavy metal contaminants in the environment with various anthropogenic and natural sources. Human health risk from heavy metal bioaccumulation in vegetables has been a subject of growing concern in recent years. To investigate Cu phytotoxic effects and bioaccumulation in the popular vegetable Chinese cabbage (Brassica pekinensis Rupr) as well as the implications for human health due to Cu in the vegetable supply, seed germination and pot culture experiments with this vegetable were carried out. Six levels (0, 0.008, 0.031, 0.125, 0.5, and 2.0 mM/L) and 3 levels (0, 0.2, and 1.0 mM/kg) of Cu treatments were performed for the seed germination and pot culture experiments, respectively. The LC(50) of Cu for seed germination of Chinese cabbage was 0.348 mM/L. In the pot culture experiments, Cu treatments significantly increased electrolyte leakage and peroxidase activity of shoot tissues, demonstrating Cu phytotoxicity to the plants. On the other hand, Cu treatments significantly stimulated, instead of reduced, chlorophyll content. Cu treatments did not show a significant effect on shoot biomass. Compared to the control, Cu treatments significantly elevated the Cu content of the shoots-9.9, 42.5, and 119.0 mg/kg (DW) of Cu were detected in the 0, 0.2, and 1.0 mM/kg treatments, respectively. These results showed that although the plants accumulated an elevated copper content and suffered damage to some extent under Cu treatment, they looked healthy. It was suggested that Chinese cabbage with an elevated Cu content and without showing visible symptoms of damage possibly could cause a risk to human health from the transfer of the metal in food.

The Impact of Water Quality, Corrosion Inhibitors and Plumbing Age on Copper Release in Distribution Systems

EPA Science Inventory

The U.S. Environmental Protection Agency promulgated the Lead and Copper Rule (LCR) in 1991, which established a copper action level of 1.3 mg/L in the consumers’ tap water. As a result, researchers have examined the effects of water chemistry on the solubility of copper to esta...

Evaluating the Mechanism of Oxalate Synthesis of Fibroporia Radiculosa Isolates Adapting to Copper-Tolerance

Treesearch

Katie Marie Jenkins

2012-01-01

Despite the drawbacks associated with tolerant organisms, copper is still used as the key component in current wood preservatives. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate in response to copper. The biosynthesis of oxalate has been connected to specific enzymes in the glyoxylate and...

A multicopper oxidase-related protein is essential for insect viability, longevity and ovary development.

PubMed

Peng, Zeyu; Green, Peter G; Arakane, Yasuyuki; Kanost, Michael R; Gorman, Maureen J

2014-01-01

Typical multicopper oxidases (MCOs) have ten conserved histidines and one conserved cysteine that coordinate four copper atoms. These copper ions are required for oxidase activity. During our studies of insect MCOs, we discovered a gene that we named multicopper oxidase-related protein (MCORP). MCORPs share sequence similarity with MCOs, but lack many of the copper-coordinating residues. We identified MCORP orthologs in many insect species, but not in other invertebrates or vertebrates. We predicted that MCORPs would lack oxidase activity due to the absence of copper-coordinating residues. To test this prediction, we purified recombinant Tribolium castaneum (red flour beetle) MCORP and analyzed its enzymatic activity using a variety of substrates. As expected, no oxidase activity was detected. To study MCORP function in vivo, we analyzed expression profiles of TcMCORP and Anopheles gambiae (African malaria mosquito) MCORP, and assessed RNAi-mediated knockdown phenotypes. We found that both MCORPs are constitutively expressed at a low level in all of the tissues we analyzed. Injection of TcMCORP dsRNA into larvae resulted in 100% mortality prior to adult eclosion, with death occurring mainly during the pharate pupal stage or late pharate adult stage. Injection of TcMCORP dsRNA into pharate pupae resulted in the death of approximately 20% of the treated insects during the pupal to adult transition and a greatly shortened life span for the remaining insects. In addition, knockdown of TcMCORP in females prevented oocyte maturation and, thus, greatly decreased the number of eggs laid. These results indicate that TcMCORP is an essential gene and that its function is required for reproduction. An understanding of the role MCORP plays in insect physiology may help to develop new strategies for controlling insect pests.

Assessing copper thresholds for phytotoxicity and potential dietary toxicity in selected vegetable crops.

PubMed

Yang, Xiao-E; Long, Xin-Xian; Ni, Wu-Zhong; Ye, Zhen-Qian; He, Zhen-Li; Stoffella, Peter J; Calvert, David V

2002-11-01

Copper pollution in soils is widespread, and its accumulation in crop products could pose a risk on human health. In this paper, bioavailability of added copper (Cu) and critical Cu concentrations in a vegetable garden soil was evaluated for Chinese cabbage (Brassica chinensis L.), pakchoi (Brassica chinensis L.), and celery (Apiumg graveolens L. var. dulce DC) based on human dietary toxicity. The availability of added Cu in the soil decreased with incubation time, and had minimal change after 10-12 weeks. After incubated for 12 weeks, about 60% of added Cu was not extractable by DTPA. The same crops were also grown in sand culture to determine their responses to solution Cu. Shoot growth was significantly inhibited at Cu concentrations above 10 mg kg(-1) in the solution or above 150 mg kg(-1) (DTPA-Cu) in the soil. The sensitivity of the crops to Cu toxicity differed among the three vegetable crops. Copper concentration in shoots and edible parts varied with Cu supply levels and type of the vegetables. Negative correlations (r=-0.90-0.99**) were noted between Cu concentration in shoots and fresh matter yields, but Cu concentrations in the edible parts were positively correlated with available and total Cu in the soil (r=0.91-0.99**). The critical tissue Cu concentrations at 10% shoot DM reduction were 19.4, 5.5, 30.9 mg kg(-1) for Chinese cabbage, pakchoi, and celery, respectively. Based on the threshold of human dietary toxicity for Cu (10 mg kg(-1)), the critical concentrations of total and available Cu in the soil were 430 and 269 mg kg(-1) for pakchoi, 608 and 313 mg kg(-1) for celery, and 835 and 339 mg kg(-1) for Chinese cabbage, respectively.

Accumulation of heavy metals in freshwater fish in cage aquaculture at Cirata Reservoir, West Java, Indonesia.

PubMed

Salami, Indah Rachmatiah Siti; Rahmawati, Suphia; Sutarto, Ratri Indri Hapsari; Jaya, Pinilih Marendra

2008-10-01

Freshwater fish demand in West Java is supported by cage aquaculture in reservoirs. Cirata Reservoir is one of three cascading hydropower reservoirs built along the Citarum River that receives domestic and industrial wastes. Water pollution by heavy metals, such as copper and lead, increases the health risk of humans who consume the fish. The study was aimed to evaluate the concentration of copper and lead in fish, specifically on Cyprinus carpio, that are widely cultivated in the Cirata Reservoir. Two sizes of fish were collected from five sampling points around floating-cage area. The liver of the fish was found to contain the highest copper level, followed by gills, skin, and muscle. In contrast, lead was also high in the liver, followed by skin, gills, and the muscle, but the copper concentration found in the tissues studied was much higher (31.111 +/- 17.911 mg/kg dry wt) than the lead content (0.290 +/- 0.346 mg/kg dry wt). The concentration of metals in smaller fish was always higher than than that in bigger fish. The metals content was also compared to those in fish exposed in a semistatic laboratory-scale study using Oreochromis niloticus. After 28 days exposure with 0.01 mg Cu/L, fish accumulated 21.53 mg Cu/kg dry wt, whereas for Pb exposure of 0.016 mg/L, fish accumulated up to 7 mg/kg dry wt. However, estimates of Cu and Pb intake from C. carpio consumption were still below the average daily intake (ADI) limit. This study suggested that monitoring of water quality and heavy metals in cultured fish is important in protecting human health.

Antioxidant status and mineral contents in tissues of rutin and baicalin fed rats.

PubMed

Gao, Zhonghong; Xu, Huibi; Chen, Xiaojun; Chen, Hao

2003-08-08

The versatile benefit effects of flavonoids lead some nutritionists to believe that they are micronutrients. However, excess intake of flavonoids may cause side effects. In this paper, the effects produced by a higher intake of rutin and baicalin on antioxidant status as well as trace minerals such as iron, copper and zinc in rat tissues were studied. When rats were fed a rutin or baicalin containing diet (1%) for 20 days, the body weight gain was lower than that of the control group. Both rutin and baicalin caused significant a decrease of catalase activity and a moderate increase of total superoxide dismutase activity in the liver. The total antioxidant status of flavonoid fed rats was increased in the liver but decreased in the serum. In comparison to the control group, the lipid peroxidation level in the liver of the rutin fed group was significantly decreased; however, there was no statistical significance in the liver of the baicalin fed group and the brain of both flavonoids groups. The liver homogenates of both flavonoid fed rats significantly inhibited alkyl radical-induced lipid peroxidation. The iron contents in the liver of flavonoid fed rats were significantly decreased; rutin also caused zinc and copper decrease in the liver. These results indicated that high flavonoid intake can improve rat antioxidant systems in the liver; while it can also cause a trace mineral decrease and, in turn, reduce the activities of some metal-containing enzymes and may cause harmful effects on health.

Evaluating the Anticancer Properties of Liposomal Copper in a Nude Mouse Xenograft Model of Human Prostate Cancer: Formulation, In Vitro, In Vivo, Histology and Tissue Distribution Studies

PubMed Central

Wang, Yan; Zeng, San; Lin, Tien-Min; Krugner-Higby, Lisa; Lyman, Doug; Steffen, Dana; Xiong, May P.

2014-01-01

Purpose Although copper (Cu) complexes have been investigated as anticancer agents, there has been no description of Cu itself as a cancer killing agent. A stealth liposomal Cu formulation (LpCu) was studied in vitro and in vivo. Methods LpCu was evaluated in prostate cancer origin PC-3 cells by a metabolic cytotoxicity assay, by monitoring reactive oxygen species (ROS), and by flow cytometry. LpCu efficacy was evaluated in vivo using intratumoral and intravenous injections into mice bearing PC-3 xenograft tumors. Toxicology was assessed by performing hematological and blood biochemistry assays, and tissue histology and Cu distribution was investigated by elemental analysis. Results LpCu and free Cu salts displayed similar levels of cell metabolic toxicity and ROS. Flow cytometry indicated that the mechanisms of cell death were both apoptosis and necrosis. Animals injected i.t. with 3.5 mg/kg or i.v. with 3.5 and 7.0 mg/kg LpCu exhibited significant tumor growth inhibition. Kidney and eye were the main organs affected by Cu-mediated toxicities, but spleen and liver were the major organs of Cu deposition. Conclusions LpCu was effective at reducing tumor burden in the xenograft prostate cancer model. There was histological evidence of Cu toxicity in kidneys and eyes of animals treated at the maximum tolerated dose of LpCu 7.0 mg/kg. PMID:24848339

Heavy metal concentrations in the tissue of Sparus sarba Forskal, 1775 from the United Arab Emirates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Ghais, S.M.

1995-10-01

Pollution of the marine environment by inorganic and organic chemicals has been recognised as one of the major factors posing serious threat to the survival of marine organisms including fish. Heavy metal contamination of the marine environment has been reported to cause toxicity to aquatic organisms. Natural processes such as volcanic eruptions, erosion and wind, industrial activities and mining are the major sources of metal contamination. Exposure to heavy metals through air, water and/or the food chain is known to induce a wide variety of toxic effects in humans and animals. Metals such as zinc manganese and copper are toxicmore » only when present in high enough amounts, but at low levels are considered essential as micronutients. Extensive studies have been carried out in Europe and America to determine toxicity and bio-accumulation of these metals in fish and other marine flora and fauna. However, there is a gap in our knowledge of the kind and extent of marine pollution by heavy metals around the coast of the United Arab Emirates (UAE) and the resultant contamination of the aquatic habitat. This study was designed to investigate the concentrations of cadmium, cobalt, copper, manganese, nickel, lead and zinc in the muscle, liver and heart, and mercury in the muscle tissue of Sparus Sarba, one of the more nutritionally popular fish of the UAE region. 11 refs., 3 figs., 2 tabs.« less

Evaluating blood and excrement as bioindicators for metal accumulation in birds.

PubMed

Berglund, Åsa M M

2018-02-01

Birds are widely used to assess metal contamination in the environment and there are different approaches to determine the exposure level in individuals, some being destructive (collection of soft tissues) and some non-destructive (blood, feathers and excrement). The use of blood to detect internal concentrations of metals is an acknowledged method, but to what extent blood can predict the concentrations in soft tissues has been less well evaluated in wild terrestrial birds. The same is true for excrements. This study compares the non-destructive methods using blood and excrement with liver sampling, with respect to exposure and accumulation of the elements arsenic, cadmium, copper, lead and zinc in nestling pied flycatchers (Ficedula hypoleuca). Blood, liver and excrement reflected the environmental exposure of non-essential elements and were independent of nestling sex. There were asymptotic relationships between the concentration of arsenic, cadmium and lead in liver and blood, excrement and liver, and excrement and blood, but none for copper or zinc. Those relationships were generally stronger between liver and blood than between excrements and internal concentrations. Lead had the strongest associations for all matrixes. The conclusion is that blood is an appropriate tool to assess accumulation of arsenic, cadmium and especially lead, but that blood can underestimate the accumulation at highly contaminated sites. Excrement can also give an indication of metal accumulation, but may overestimate internal concentrations at high exposure, and individual variability makes direct comparisons between these matrices less appropriate. Copyright © 2017 Elsevier Ltd. All rights reserved.

COPPER RESEARCH UPDATE

EPA Science Inventory

This presentation provides an update and overview of new research results and remaining research needs with respect to copper corrosion control issues. The topics to be covered include: occurrence of elevated copper release in systems that meet the Action Level; impact of water c...

Chemical contaminants in gray whales (eschichtius robustus) stranded in Alaska, Washington, and California, USA. Technical memo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varanasi, U.; Stein, J.E.; Tilbury, K.L.

1993-08-01

The concentrations of chlorinated hydrocarbons (CHs) such as polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethanes (DDTs), 1,1-dichloro-2,2-bis(p- chlorophenyl) ethenes (DDEs), and chlordanes, and essential (e.g., zinc, selenium, copper) and toxic (e.g., mercury, lead) elements were measured in tissues and stomach contents from 22 gray whales (Eschrichtius robustus) stranded between 1988 and 1991. The stranding sites ranged from the relatively pristine areas of Kodiak Island, Alaska, to more urbanized areas in Puget Sound, Washington, and San Francisco Bay, California, with the majority of the sites on the Washington outer coast and in Puget Sound. Similar to concentrations in tissues, no significant differences weremore » observed in concentrations of elements in stomach contents between whales stranded in Puget Sound and whales stranded at the more pristine sites. The lack of data from apparently healthy gray whales limits the assessment of whether the levels of anthropogenic contaminants found in tissues may have deleterious effects on the health of gray whales.« less

Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model.

PubMed

Pereira, Talita Carneiro Brandão; Campos, Maria Martha; Bogo, Maurício Reis

2016-07-01

Copper is an essential micronutrient and a key catalytic cofactor in a wide range of enzymes. As a trace element, copper levels are tightly regulated and both its deficit and excess are deleterious to the organism. Under inflammatory conditions, serum copper levels are increased and trigger oxidative stress responses that activate inflammatory responses. Interestingly, copper dyshomeostasis, oxidative stress and inflammation are commonly present in several chronic diseases. Copper exposure can be easily modeled in zebrafish; a consolidated model in toxicology with increasing interest in immunity-related research. As a result of developmental, economical and genetic advantages, this freshwater teleost is uniquely suitable for chemical and genetic large-scale screenings, representing a powerful experimental tool for a whole-organism approach, mechanistic studies, disease modeling and beyond. Copper toxicological and more recently pro-inflammatory effects have been investigated in both larval and adult zebrafish with breakthrough findings. Here, we provide an overview of copper metabolism in health and disease and its effects on oxidative stress and inflammation responses in zebrafish models. Copper-induced inflammation is highlighted owing to its potential to easily mimic pro-oxidative and pro-inflammatory features that combined with zebrafish genetic tractability could help further in the understanding of copper metabolism, inflammatory responses and related diseases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Modulation of cholesterol levels in broiler meat by dietary garlic and copper.

PubMed

Konjufca, V H; Pesti, G M; Bakalli, R I

1997-09-01

Male Ross x Ross 208 chickens were fed from hatching to 21 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 0, 1.5, 3.0, and 4.5% of a commercial garlic powder in Experiments 1 and 2. Once the dose-response relationship was established, 3% garlic powder or 63 or 180 mg/kg copper as cupric citrate or cupric sulfate pentahydrate were supplemented to the diet (Experiments 3, 4, 5, and 6). In the first two experiments, reductions of plasma cholesterol (P = 0.006) and triacylglycerols (P = 0.013) and liver (P = 0.012) and breast muscle (P = 0.165) cholesterol were observed in garlic-supplemented birds. Feeding either garlic powder or copper (63 and 180 mg/kg) resulted in reduced levels of plasma cholesterol, liver cholesterol, blood reduced glutathione, and breast and thigh muscle cholesterol. Differences were significant at P < 0.05 in at least one experiment. 3-Hydroxy-3-methylglutaryl reductase activity was decreased due to dietary garlic (P = 0.0369), but not by pharmacological levels of dietary copper (P = 0.982). The activity of fatty acid synthetase was decreased in birds fed copper (P = 0.035). Both garlic and copper supplements decreased cholesterol 7 alpha-hydroxylase activity (P = 0.024 and P = 0.022, respectively). The results of these trials confirm the findings that garlic and copper alter lipid and cholesterol metabolism. However, they do not work by the same mechanism. Feeding dietary garlic or copper for 21 d reduced cholesterol levels of broiler meat without altering growth of the chickens or feed efficiency.

Altered serum copper homeostasis suggests higher oxidative stress and lower antioxidant capability in patients with chronic hepatitis B.

PubMed

Huang, Yansong; Zhang, Yuan; Lin, Zhexuan; Han, Ming; Cheng, Hongqiu

2018-06-01

Copper homeostasis can be altered by inflammation. This study aimed to investigate the alteration of serum copper homeostasis and to explore its clinical significance in patients with chronic hepatitis B (CHB).Thirty-two patients with CHB and 10 aged- and sex-matched healthy controls were recruited. Analyses included serum levels of total copper (TCu), copper ions (Cu), small molecule copper (SMC), ceruloplasmin (CP), Cu/Zn superoxide dismutase 1 (SOD1), urinary copper, and the activities of serum CP and SOD1.The serum TCu and urinary copper levels in patients with CHB were significantly higher than the controls (P = .04 and .003), while the serum Cu was lower than the controls (P = .0002). CP and SOD1 activities in the serum were significantly lower in patients with CHB compared to controls (P = .005) despite higher serum concentrations. In addition, serum alanine aminotransferase inversely correlated with serum CP activity (P = .0318, r = -0.4065).Serum copper homeostasis was altered in this cohort of patients with CHB. The results suggest increased oxidative stress and impaired antioxidant capability in patients with CHB, in addition to necroinflammation. These results may provide novel insights into the diagnosis and treatment of patients with CHB.

Subchronic treatment of rats with aurothioglucose; effects on plasma, hepatic, renal and urinary zinc, copper and metallothionein.

PubMed

McVety, K J; Shaikh, Z A

1987-11-01

Administration of sodium aurothioglucose (10 mg/kg per day) to female rats for up to 8 weeks resulted in no apparent effects on the kidney. Gold accumulated in kidney, liver, spleen, pancreas, skin and blood. Although plasma and hepatic gold levels increased with time, no remarkable change in either copper, zinc or metallothionein (MT) levels was observed. Gel filtration chromatography of plasma showed binding of gold to albumin, whereas copper was associated with albumin, ceruloplasmin and a protein eluting in the void volume of the Sephadex G-150 column. Almost all of the hepatic gold was bound to proteins other than MT. In the kidney, not only gold but also copper and MT increased rapidly, reached a maximum between 2 and 4 weeks and exhibited insignificant change thereafter. Gold-treated animals showed an increase in binding of copper to the very high molecular weight plasma protein, which may be involved in transport of copper to the kidneys. Urinary gold and MT followed a pattern similar to that in the kidney. Renal zinc also increased but returned to normal by week 8. In renal cytosol 57% and 54% of the gold and copper, respectively, were associated with MT. It appears that the elevated levels of copper and zinc, rather than gold, are responsible for the induction of MT synthesis. This then provides a mechanism by which gold and the inducing metals are retained by the kidney.

Laser synthesis of a copper-single-walled carbon nanotube nanocomposite via molecular-level mixing and non-equilibrium solidification

NASA Astrophysics Data System (ADS)

Tu, Jay F.; Rajule, Nilesh; Molian, Pal; Liu, Yi

2016-12-01

A copper-single-walled carbon nanotube (Cu-SWCNT) metal nanocomposite could be an ideal material if it can substantially improve the strength of copper while preserving the metal’s excellent thermal and electrical properties. However, synthesis of such a nanocomposite is highly challenging, because copper and SWCNTs do not form intermetallic compounds and are insoluble; as a result, there are serious issues regarding wettability and fine dispersion of SWCNTs within the copper matrix. In this paper we present a novel wet process, called the laser surface implantation process (LSI), to synthesize Cu-SWCNT nanocomposites by mixing SWCNTs into molten copper. The LSI process includes drilling several microholes on a copper substrate, filling the microholes with SWCNTs suspended in solution, and melting the copper substrate to create a micro-well of molten copper. The molten copper advances radially outward to engulf the microholes with pre-deposited SWCNTs to form the Cu-SWCNT implant upon solidification. Rapid and non-equilibrium solidification is achieved due to copper’s excellent heat conductivity, so that SWCNTs are locked in position within the copper matrix without agglomerating into large clusters. This wet process is very different from the typical dry processes used in powder metallurgy. Very high hardness improvement, up to 527% over pure copper, was achieved, confirmed by micro-indentation tests, with only a 0.23% SWCNT volume fraction. The nanostructure of the nanocomposite was characterized by TEM imaging, energy-dispersive x-ray spectroscopy mapping and spectroscopy measurements. The SWCNTs were found to be finely dispersed within the copper matrix with cluster sizes in the range of nanometers, achieving the goal of molecular-level mixing.

Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma.

PubMed

Merza, Hussein; Sood, Neha; Sood, Raman

2015-10-01

Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations.

Response to copper and sodium chloride excess in Spirulina sp. (cyanobacteria).

PubMed

Deniz, F; Saygideger, S D; Karaman, S

2011-07-01

Physiological responses of the cyanobacterium, Spirulina sp., were evaluated following exposure to copper (0.1 and 1.0 mg/L) and sodium chloride (0.2 and 0.4 mol/L) for 7 days. Growth and chlorophyll a content exhibited decreases at most exposure levels, while increases occurred for malondialdehyde at all exposure levels. Proline content was increased at the higher exposure levels. Carotenoid levels of Spirulina sp. were not significantly changed. Increased amounts of malondialdehyde were indicative of free radical formation in Spirulina sp. under the stress, while increasing levels of proline pointed to the occurrence of a scavenging mechanism. Concentrations of copper in Spirulina sp. decreased with increasing concentrations of NaCl.

Trace elements and organic compounds in streambed sediment and aquatic biota from the Sacramento River Basin, California, October and November 1995

USGS Publications Warehouse

MacCoy, Dorene E.; Domagalski, Joseph L.

1999-01-01

Elevated levels of trace elements and hydrophobic organic compounds were detected in streambed sediments and aquatic biota [Asiatic clam (Corbicula fluminea) or bottom-feeding fish] of the Sacramento River Basin, California, during October and November 1995. Trace elements detected included cadmium, copper, mercury, lead, and zinc. Elevated levels of cadmium, copper, and zinc in the upper Sacramento River are attributed to a mining land use, and elevated levels of zinc and lead in an urban stream, and possibly in the lower Sacramento River, are attributed to urban runoff processes. Elevated levels of mercury in streambed sediment are attributed to either past mercury mining or to the use of mercury in past gold mining operations. Mercury mining was an important land use within the Coast Ranges in the past and gold mining was an important land use of the Sierra Nevada in the past. Mercury was the only trace element found in elevated levels in the tissue of aquatic biota, and those levels also could be attributed to either mining or urban runoff. Hydrophobic organic compounds also were detected in streambed sediments and aquatic biota. The most frequently detected compounds were DDT and its breakdown products, dieldrin, oxychlordane, and toxaphene. Differences were found in the types of compounds detected at agricultural sites and the urban site. Although both types of sites had measurable concentrations of DDT or its breakdown products, the urban site also had measurable concentrations of pesticides used for household pest control. Few semivolatile compounds were detected in the streambed sediments of any site. The semivolatile compound p-cresol, a coal-tar derivative associated with road maintenance, was found in the highest concentration.

Copper poisoning in a dairy herd fed a mineral supplement

PubMed Central

Bradley, Charles H.

1993-01-01

Copper poisoning in a dairy herd resulted in the death of 9 of 63 (14%) adult Holstein cows. Clinical signs were acute anorexia, weakness, mental dullness, poor pupillary light reflexes, and scant nasal discharge. These were followed by recumbency, chocolate-colored blood, jaundice, and death. Four animals exhibited signs of hyperesthesia and/or rumen stasis prior to death. At necropsy there was generalized icterus of body tissues, with the liver appearing orange and the kidneys dark blue. Histologically, there was accumulation of hemosiderin in Kupffer cells, and severe to moderate hepatocellular necrosis in all cases. Ammonium molybdate added to the ration, combined with the cessation of mineral supplementation, arrested the outbreak. These cases illustrate significant mortality, due to copper poisoning, in adult cattle fed a low-dose mineral dietary supplement for over two years. Dietary copper intake of the herd (on a dry matter basis) was 37.5 mg/kg for lactating cows and 22.6 mg/kg for dry cows. PMID:17424221

Chaperones CCS, ATOX and COXIV responses to copper supplementation in healthy adults.

PubMed

Araya, Magdalena; Andrews, Monica; Pizarro, Fernando; Arredondo, Miguel

2012-04-01

Assessment of proteins in blood and other tissues has failed to identify markers of early copper effects on health. Studies in animal models show that chaperone of SOD (CCS) respond to changes of copper status. Evidence about other copper chaperones (COXIV, ATOX) is not clear. The aim of this study was to assess by means of an in vitro challenge the mRNA relative abundance of ccs, sod1, coxIV, mtIIa and atox in peripheral mononuclear cells (PMNCs) obtained from healthy individuals, acutely and chronically supplemented with small-to-moderate amounts of copper. Healthy participants received 8 mg Cu/d (supplemented group, SG) or placebo, (placebo group, PG) for 2 months. Biochemical indicators were assessed at basal (T0) and after 2 (T2) and 60 days (T60). At these times PMNCs were obtained, challenged with 1, 5 or 20 μM Cu-histidine for 20 h and the mRNA relative abundance of the selected genes assessed by real time PCR. The results showed that at T0, intracellular copper was not different between experimental and control groups. This increased at T2 and T60 when the copper in the media increased (two-way ANOVA, P < 0.001). In PG, CCS mRNA transcripts showed no significant changes (two-way ANOVA) at T2 and T60. In SG, CCS changed by treatment, time and interaction (two-way ANOVA, all P < 0.001). SOD, ATOX and COXIV expressions changed in both PG and SG showing various patterns of response, requiring further study. MTII responded as expected. We conclude that using healthy individuals as a human model, CCS but not SOD, ATOX or COXIV responded consistently to controlled changes of copper availability in an in vitro copper challenge.

Effect of copper on the scope for growth of clams (Tapes philippinarum) from a farming area in the Northern Adriatic Sea.

PubMed

Munari, Cristina; Mistri, Michele

2007-09-01

Copper is currently the most common biocide in antifouling paints. Levels of this metal were measured in the water, particulate matter and sediments from a shellfish farming area in the Sacca di Goro (Northern Adriatic Sea) over one year. With respect to the 1980s, copper environmental level increased twofold. The release of copper from shellfish farmers' boats was also estimated to be > 250 kg Cu y(-1). Clams Tapes philippinarum were collected in the same area and seasonally exposed to a sublethal (10 microg Cu l(-1)) concentration of copper. Physiological traits were significantly affected by copper exposure (scope for growth declined as a result of reduced clearance rate, increased oxygen consumption and a generally lower absorption efficiency). The results of this study are cause for concern for shellfish farming activities at least in Northern Adriatic, where shellfish farming is a monoculture of T. philippinarum. A strict interpretation of the precautionary principle might suggest that more rigorous regulatory action to control copper inputs in the field would be justified.

Effects of Copper Pollution on the Phenolic Compound Content, Color, and Antioxidant Activity of Wine.

PubMed

Sun, Xiangyu; Ma, Tingting; Han, Luyang; Huang, Weidong; Zhan, Jicheng

2017-05-03

The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, and the antioxidant activity values of the wine also increased. When the copper concentration reached the lowest level of the medium copper range (9.6~16 mg/L), most of the indices also improved. When the copper concentrations reached the latter part of the medium copper range (19.2 and 22.4 mg/L), many of the tested indices began to decrease. Furthermore, when the copper concentration reached the high ranges (32, 64, and 96 mg/L), the polyphenol content, CIELAB color parameters, and antioxidant activity of wine were substantially decreased, indicating the need to control increasing copper content in grape must.

Gastrointestinal upsets associated with ingestion of copper-contaminated water.

PubMed Central

Knobeloch, L; Ziarnik, M; Howard, J; Theis, B; Farmer, D; Anderson, H; Proctor, M

1994-01-01

During 1992 and 1993 the Wisconsin Division of Health investigated five cases in which copper-contaminated drinking water was suspected of causing gastrointestinal upsets. Each of these case studies was conducted after our office was notified of high copper levels in drinking water or notified of unexplained illnesses. Our findings suggest that drinking water that contains copper at levels above the federal action limit of 1.3 mg/l may be a relatively common cause of diarrhea, abdominal cramps, and nausea. These symptoms occurred most frequently in infants and young children and among resident of newly constructed or renovated homes. Images p958-a PMID:9738210

Composite vascular scaffold combining electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves structure.

PubMed

Liu, Yuanyuan; Jiang, Chen; Li, Shuai; Hu, Qingxi

2016-08-01

While the field of tissue engineered vascular grafts has greatly advanced, many inadequacies still exist. Successfully developed scaffolds require mechanical and structural properties that match native vessels and optimal microenvironments that foster cell integration, adhesion and growth. We have developed a small diameter, three-layered composite vascular scaffold which consists of electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves by combining the electrospinning and dip-coating methods. Scaffold morphology and mechanics were assessed, quantified and compared to native vessels. Scaffolds were seeded with Human Umbilical Vein Endothelial Cells (HUVECs), cultured in vitro for 3 days and were evaluated for cell viability and morphology. The results showed that composite scaffolds had adjustable mechanical strength and favorable biocompatibility, which is important in the future clinical application of Tissue-engineered vascular grafts (TEVGs). Copyright © 2016 Elsevier Ltd. All rights reserved.

Copper, Zinc Superoxide Dismutase is Primarily a Cytosolic Protein in Human Cells

NASA Astrophysics Data System (ADS)

Crapo, James D.; Oury, Tim; Rabouille, Catherine; Slot, Jan W.; Chang, Ling-Yi

1992-11-01

The intracellular localization of human copper, zinc superoxide dismutase (Cu,Zn-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) was evaluated by using EM immunocytochemistry and both isolated human cell lines and human tissues. Eight monoclonal antibodies raised against either native or recombinant human Cu,Zn-SOD and two polyclonal antibodies raised against either native or recombinant human Cu,Zn-SOD were used. Fixation with 2% paraformaldehyde/0.2% glutaraldehyde was found necessary to preserve normal distribution of the protein. Monoclonal antibodies were less effective than polyclonal antibodies in recognizing the antigen after adequate fixation of tissue. Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus, consistent with it being a soluble cytosolic protein. Mitochondria and secretory compartments did not label for this protein. In human cells, peroxisomes showed a labeling density slightly less than that of cytoplasm.

The association between serum copper concentrations and cardiovascular disease risk factors in children and adolescents in NHANES.

PubMed

Zang, Xiaodong; Huang, Hesuyuan; Zhuang, Zhulun; Chen, Runsen; Xie, Zongyun; Xu, Cheng; Mo, Xuming

2018-06-01

Copper is an essential element in human beings, alterations in serum copper levels could potentially have effect on human health. To date, no data are available regarding how serum copper affects cardiovascular disease (CVD) risk factors in children and adolescents. We examined the association between serum copper levels and CVD risk factors in children and adolescents. We analyzed data consisting of 1427 subjects from a nationally representative sample of the US population in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The CVD risk factors included total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure. Multivariate and generalized linear regressions were performed to investigate associations adjusted for age, gender, ethnicity, poverty:income ratio (PIR), BMI, energy intake, and physical activity. We found significant associations between serum copper and total cholesterol (coefficient = 0.132; 95% CI 0.081, 0.182; P for trend < 0.001), glycohemoglobin (coefficient = 0.044; 95% CI 0.020, 0.069; P < 0.001), and fasting insulin (coefficient = 0.730; 95% CI 0.410, 1.050; P < 0.001) among the included participants. Moreover, in the generalized linear models, subjects with the highest copper levels demonstrated a 0.83% (95% CI 0.44%, 1.24%) greater increase in serum total cholesterol (p for trend < 0.001) when compared to participants with the lowest copper concentrations. Our results provide the first epidemiological evidence that serum copper concentrations are associated with total cholesterol concentrations in children and adolescents. However, the underlying mechanisms still need further exploration.

Copper tolerance in Frankia sp. strain EuI1c involves surface binding and copper transport.

PubMed

Rehan, Medhat; Furnholm, Teal; Finethy, Ryan H; Chu, Feixia; El-Fadly, Gomaah; Tisa, Louis S

2014-09-01

Several Frankia strains have been shown to be copper-tolerant. The mechanism of their copper tolerance was investigated for Frankia sp. strain EuI1c. Copper binding was shown by binding studies. Unusual globular structures were observed on the surface of the bacterium. These globular structures were composed of aggregates containing many relatively smaller "leaf-like" structures. Scanning electron microscopy with energy-dispersive X-ray (SEM-EDAX) analysis of these structures indicated elevated copper and phosphate levels compared to the control cells. Fourier transform infrared spectroscopy (FTIR) analysis indicated an increase in extracellular phosphate on the cell surface of copper-stressed cells. Bioinformatics' analysis of the Frankia sp. strain EuI1c genome revealed five potential cop genes: copA, copZ, copC, copCD, and copD. Experiments with Frankia sp. strain EuI1c using qRT-PCR indicated an increase in messenger RNA (mRNA) levels of the five cop genes upon Cu(2+) stress. After 5 days of Cu(2+) stress, the copA, copZ, copC, copCD, and copD mRNA levels increased 25-, 8-, 18-, 18-, and 25-fold, respectively. The protein profile of Cu(2+)-stressed Frankia sp. strain EuI1c cells revealed the upregulation of a 36.7 kDa protein that was identified as FraEuI1c_1092 (sulfate-binding periplasmic transport protein). Homologues of this gene were only present in the genomes of the Cu(2+)-resistant Frankia strains (EuI1c, DC12, and CN3). These data indicate that copper tolerance by Frankia sp. strain EuI1c involved the binding of copper to the cell surface and transport proteins.

ROS dependent copper toxicity in Hydra-biochemical and molecular study.

PubMed

Zeeshan, Mohammed; Murugadas, Anbazhagan; Ghaskadbi, Surendra; Rajendran, Ramasamy Babu; Akbarsha, Mohammad Abdulkader

2016-01-01

Copper, an essential microelement, is known to be toxic to aquatic life at concentrations higher than that could be tolerated. Copper-induced oxidative stress has been documented in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied in the lower invertebrates. The objective of the present study has been to find the effect of ROS-mediated toxicity of environmentally relevant concentrations of copper at organismal and cellular levels in Hydra magnipapillata. Exposure to copper at sublethal concentrations (0.06 and 0.1mg/L) for 24 or 48h resulted in generation of significant levels of intracellular reactive oxygen species (ROS). We infer that the free radicals here originate predominantly at the lysosomes but partly at the mitochondria also as visualized by H2-DHCFDA staining. Quantitative real-time PCR of RNA extracted from copper-exposed polyps revealed dose-dependent up-regulation of all antioxidant response genes (CAT, SOD, GPx, GST, GR, G6PD). Concurrent increase of Hsp70 and FoxO genes suggests the ability of polyps to respond to stress, which at 48h was not the same as at 24h. Interestingly, the transcript levels of all genes were down-regulated at 48h as compared to 24h incubation period. Comet assay indicated copper as a powerful genotoxicant, and the DNA damage was dose- as well as duration-dependent. Western blotting of proteins (Bax, Bcl-2 and caspase-3) confirmed ROS-mediated mitochondrial cell death in copper-exposed animals. These changes correlated well with changes in morphology, regeneration and aspects of reproduction. Taken together, the results indicate increased production of intracellular ROS in Hydra on copper exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Basis for Antioxidant Enzymes in Mediating Copper Detoxification in the Nematode Caenorhabditis elegans

PubMed Central

Song, Shaojuan; Zhang, Xueyao; Wu, Haihua; Han, Yan; Zhang, Jianzhen; Ma, Enbo; Guo, Yaping

2014-01-01

Antioxidant enzymes play a major role in defending against oxidative damage by copper. However, few studies have been performed to determine which antioxidant enzymes respond to and are necessary for copper detoxification. In this study, we examined both the activities and mRNA levels of SOD, CAT, and GPX under excessive copper stress in Caenorhabditis elegans, which is a powerful model for toxicity studies. Then, taking advantage of the genetics of this model, we assessed the lethal concentration (LC50) values of copper for related mutant strains. The results showed that the SOD, CAT, and GPX activities were significantly greater in treated groups than in controls. The mRNA levels of sod-3, sod-5, ctl-1, ctl-2, and almost all gpx genes were also significantly greater in treated groups than in controls. Among tested mutants, the sod-5, ctl-1, gpx-3, gpx-4, and gpx-6 variants exhibited hypersensitivity to copper. The strains with SOD or CAT over expression were reduced sensitive to copper. Mutations in daf-2 and age-1, which are involved in the insulin/insulin-like growth factor-1 signaling pathway, result in reduced sensitivity to stress. Here, we showed that LC50 values for copper in daf-2 and age-1 mutants were significantly greater than in N2 worms. However, the LC50 values in daf-16;daf-2 and daf-16;age-1 mutants were significantly reduced than in daf-2 and age-1 mutants, implying that reduced copper sensitivity is influenced by DAF-16-related functioning. SOD, CAT, and GPX activities and the mRNA levels of the associated copper responsive genes were significantly increased in daf-2 and age-1 mutants compared to N2. Additionally, the activities of SOD, CAT, and GPX were greater in these mutants than in N2 when treated with copper. Our results not only support the theory that antioxidant enzymes play an important role in copper detoxification but also identify the response and the genes involved in these processes. PMID:25243607

Colloidal and electrochemical aspects of copper-CMP

NASA Astrophysics Data System (ADS)

Sun, Yuxia

Copper based interconnects with low dielectric constant layers are currently used to increase interconnect densities and reduce interconnect time delays in integrated circuits. The technology used to develop copper interconnects involves Chemical Mechanical Planarization (CMP) of copper films deposited on low-k layers (silica or silica based films), which is carried out using slurries containing abrasive particles. One issue using such a structure is copper contamination over dielectric layers (SiO2 film), if not reduced, this contamination will cause current leakage. In this study, the conditions conducive to copper contamination onto SiO2 films during Cu-CMP process were studied, and a post-CMP cleaning technique was discussed based on experimental results. It was found that the adsorption of copper onto a silica surface is kinetically fast (<0.5 minute). The amount of copper absorbed is pH and concentration dependent and affected by presence of H2O2, complexing agents, and copper corrosion inhibitor Benzotrazole. Based on de-sorption results, DI water alone was unable to reduce adsorbed copper to an acceptable level, especially for adsorption that takes place at a higher pH condition. The addition of complex agent, citric acid, proved effective in suppressing copper adsorption onto oxide silica during polishing or post-CMP cleaning by forming stable copper-CA complexes. Surface Complexation Modeling was used to simulate copper adsorption isotherms and predict the copper contamination levels on SiO2 surfaces. Another issue with the application of copper CMP is its environmental impact. CMP is a costly process due to its huge consumption of pure water and slurry. Additionally, Cu-CMP processing generates a waste stream containing certain amounts of copper and abrasive slurry particles. In this study, the separation technique electrocoagulation was investigated to remove both copper and abrasive slurry particles simultaneously. For effluent containing ˜40 ppm dissolved copper, it was found that ˜90% dissolved copper was removed from the waste streams through electroplating and in-situ chemical precipitation. The amount of copper removed through plating is impacted by membrane surface charge, type/amount of complexing agents, and solid content in the slurry suspension. The slurry particles can be removed ˜90% within 2 hours of EC through multiple mechanisms.

Review of heavy metal accumulation on aquatic environment in Northern East Mediterrenean Sea part I: some essential metals.

PubMed

Yılmaz, Ayşe Bahar; Yanar, Alper; Alkan, Ela Nur

2017-03-01

All pollutants can reach the aquatic environments and the levels of heavy metals in upper members of the food web like fish can reach values many times higher than those found in aquatic environment or in sediments. Although heavy metals are essential or non-essential, all heavy metals are potentially harmful to humans and most organisms at some level of exposure and absorption. Marine organisms are good indicators for long-term monitoring of metal accumulation. The present review study is for evaluation of the data from previous studies about the toxic effects of selected heavy metals, like essential metals (copper, zinc, iron, chromium, and manganese), on seawater, sediment, and in different tissues of aquatic animals (demersal and bentic fish, invertabres) collected from different areas in Northern East Mediterrenean Sea since the 1990s. Some concern arose from previous studies, particularly in terms of safety for human consumption. For this purpose, 86 articles and 4 theses were examined and information was collected on the table to open a forward-looking view of the pollution of studied area. In previous studies, the variations in feeding habits, habitats, and the level of copper found in edible muscles of the demersal fish species (deep water fish species, carnivore) such as Mullus barbatus barbatus, Solea lascaris, Sparus aurata were always higher than those found in pelagic (omnivore) Mugil cephalus, Liza aurata. Results show discrepancies caused by many factors; thus, more work must be done carefully.

Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma

PubMed Central

Merza, Hussein; Sood, Neha; Sood, Raman

2015-01-01

Key Clinical Message Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations. PMID:26509015

A LATENT PERIOD IN THE ACTION OF COPPER ON RESPIRATION

PubMed Central

Cook, S. F.

1926-01-01

1. When copper chloride is allowed to act on Aspergillus niger there is at first a period during which there is no change in the rate of the production of carbon dioxide, following which the rate of respiration falls. The interval of no change is called the latent period. 2. When the copper is removed from the external solution before the end of the latent period this interval is prolonged. The rate of respiration then falls to a new level below the normal level. 3. Experiments on Nitella and on Valonia indicate that the copper penetrates the cell almost immediately. 4. The length of the latent period varies inversely as a constant power of the concentration of the copper. 5. These results are explained by assuming that the copper is made active in the respiration system by means of a reversible reaction. By using appropriate velocity constants the experimental curves can be duplicated by calculated curves. PMID:19872281

Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos.

PubMed

Sussarellu, Rossana; Lebreton, Morgane; Rouxel, Julien; Akcha, Farida; Rivière, Guillaume

2018-03-01

Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying molecular mechanisms are largely unknown. This study aims to better understand whether the embryotoxic effects of copper in Crassostrea gigas could be mediated by alterations in gene expression, and the putative role of DNA methylation, which is known to contribute to gene regulation in early embryo development. For that purpose, oyster embryos were exposed to 4 nominal copper concentrations (0.1, 1, 10 and 20 μg L -1 Cu 2+ ) during early development assays. Embryotoxicity was monitored through the oyster embryo-larval bioassay at the D-larva stage 24 h post fertilization (hpf) and genotoxicity at gastrulation 7 hpf. In parallel, the relative expression of 15 genes encoding putative homeotic, biomineralization and DNA methylation proteins was measured at three developmental stages (3 hpf morula stage, 7 hpf gastrula stage, 24 hpf D-larvae stage) using RT-qPCR. Global DNA content in methylcytosine and hydroxymethylcytosine were measured by HPLC and gene-specific DNA methylation levels were monitored using MeDIP-qPCR. A significant increase in larval abnormalities was observed from copper concentrations of 10 μg L -1 , while significant genotoxic effects were detected at 1 μg L -1 and above. All the selected genes presented a stage-dependent expression pattern, which was impaired for some homeobox and DNA methylation genes (Notochord, HOXA1, HOX2, Lox5, DNMT3b and CXXC-1) after copper exposure. While global DNA methylation (5-methylcytosine) at gastrula stage didn't show significant changes between experimental conditions, 5-hydroxymethylcytosine, its degradation product, decreased upon copper treatment. The DNA methylation of exons and the transcript levels were correlated in control samples for HOXA1 but such a correlation was diminished following copper exposure. The methylation level of some specific gene regions (HoxA1, Hox2, Engrailed2 and Notochord) displayed changes upon copper exposure. Such changes were gene and exon-specific and no obvious global trends could be identified. Our study suggests that the embryotoxic effects of copper in oysters could involve homeotic gene expression impairment possibly by changing DNA methylation levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Studies on the feeding of cupric sulfate pentahydrate, cupric citrate, and copper oxychloride to broiler chickens.

PubMed

Ewing, H P; Pesti, G M; Bakalli, R I; Menten, J F

1998-03-01

Male commercial broiler strain chickens were fed either a control diet (based on corn and soybean meal) or the control diet supplemented with cupric sulfate pentahydrate, copper oxychloride, or cupric citrate in two experiments conducted in floor pens. In Experiment 1, feeding copper at 125 mg/kg diet for 42 d significantly increased broiler growth; and the response from cupric citrate was significantly better than either cupric sulfate or copper oxychloride. In Experiment 2, the inclusion of copper from cupric citrate was reduced to 63 mg/kg and the length of the experiment was increased to 56 d. Cupric sulfate pentahydrate and copper oxychloride treatments increased weight gain by 4.9% and cupric citrate increased weight gain by 9.1%. The feed conversion ratios (grams of feed:grams of gain of live birds) in the birds fed copper were not significantly different from those fed the basal diet (P > 0.05) unless corrections were made for the weights of the dead birds; the adjusted feed conversion ratios (grams of feed:grams of gain of live birds + grams of gain of mortalities) for the copper-treated birds in Experiments 1 and 2 were 5.2 and 7.6% lower, respectively, than the ratios of birds fed the basal diets. Plasma copper levels increased in supplemented chicks by 35% in Experiment 1 and 24% in Experiment 2. Liver copper levels in both experiments were increased by 26% with copper supplementation. Mortality was not affected by dietary treatment in either experiment (P > 0.05).

In situ antimicrobial behavior of materials with copper-based additives in a hospital environment.

PubMed

Palza, Humberto; Nuñez, Mauricio; Bastías, Roberto; Delgado, Katherine

2018-06-01

Copper and its alloys are effective antimicrobial surface materials in the laboratory and in clinical trials. Copper has been used in the healthcare setting to reduce environmental contamination, and thus prevent healthcare-associated infections, complementing traditional protocols. The addition of copper nanoparticles to polymer/plastic matrices can also produce antimicrobial materials, as confirmed under laboratory conditions. However, there is a lack of studies validating the antimicrobial effects of these nanocomposite materials in clinical trials. To satisfy this issue, plastic waiting room chairs with embedded metal copper nanoparticles, and metal hospital IV pools coated with an organic paint with nanostructured zeolite/copper particles were produced and tested in a hospital environment. These prototypes were sampled once weekly for 10 weeks and the viable microorganisms were analysed and compared with the copper-free materials. In the waiting rooms, chairs with copper reduced by around 73% the total viable microorganisms present, showing activity regardless of the microorganism tested. Although there were only low levels of microorganisms in the IV pools installed in operating rooms because of rigorous hygiene protocols, samples with copper presented lower total viable microorganisms than unfilled materials. Some results did not have statistical significance because of the low load of microorganisms; however, during at least three weeks the IV pools with copper had reduced levels of microorganisms by a statistically significant 50%. These findings show for the first time the feasibility of utilizing the antimicrobial property of copper by adding nanosized fillers to other materials in a hospital environment. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Transcuprein is a Macroglobulin Regulated by Copper and Iron Availability

PubMed Central

Liu, Nanmei; Lo, Louis Shi-li; Askary, S. Hassan; Jones, LaTrice; Kidane, Theodros Z.; Nguyen, Trisha Trang Minh; Goforth, Jeremy; Chu, Yu-Hsiang; Vivas, Esther; Tsai, Monta; Westbrook, Terence; Linder, Maria C.

2009-01-01

SUMMARY Transcuprein is a high affinity copper carrier in the plasma involved in the initial distribution of copper entering the blood from the digestive tract. To identify and obtain cDNA for this protein, it was purified from rat plasma by size exclusion and copper chelate affinity chromatography, and amino acid sequences were obtained. These revealed a 190 kDa glycosylated protein identified as the macroglobulin, α1inhibitorIII, the main macroglobulin of rodent blood plasma. Albumin (65 kDa) co-purified in variable amounts and was concluded to be a contaminant (although it transiently can bind the macroglobulin). The main macroglobulin in human blood plasma (α2-macroglobulin), homologous to α1inhibitorIII, also bound copper tightly. Expression of α1I3 (transcuprein) mRNA by the liver was examined in rats with and without copper deficiency, using quantitative PCR and Northern analysis. Protein expression was examined by Western blotting. Deficient rats with 40% less ceruloplasmin oxidase activity and liver copper concentrations expressed about twice as much α1I3 mRNA, but circulating levels of transcuprein did not differ. Iron deficiency, which increased liver copper concentrations 3-fold, reduced transcuprein mRNA expression and 7circulating levels of transcuprein relative to what occurred in rats with normal or excess iron. We conclude that transcupreins are specific macroglobulins that not only carry zinc but also transport copper in the blood; and that their expression can be modulated by copper and iron availability. PMID:17363239

Effects of copper on growth, metamorphosis and endocrine disruption of Bufo gargarizans larvae.

PubMed

Wang, Chao; Liang, Gang; Chai, Lihong; Wang, Hongyuan

2016-01-01

Chinese toad (Bufo gargarizans) tadpoles were exposed to copper (1, 6.4, 32 and 64μgL(-1) copper) from the beginning of larval period through completion of metamorphosis. We examined the effects of chronic copper exposure on mortality, growth, time to metamorphosis, tail resorption time, body size at the metamorphic climax (Gs 42) and completion of metamorphosis (Gs 46) and thyroid gland histology. In addition, type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. Our result showed that 6.4-64μgL(-1) copper concentration increased the mortality and inhibited the growth of B. gargarizans tadpoles. In addition, significant reduction in size at Gs 42 and a time delay to Gs 42 were observed at 6.4-64μgL(-1) copper treatments. Moreover, histological examinations have clearly revealed that 64μgL(-1) copper caused follicular cell hyperplasia in thyroid gland. According to real-time PCR results, exposure to 32 and 64μgL(-1) copper significantly up-regulated mRNA expression of Dio3, but down-regulated mRNA expression of TRα and TRβ mRNA level. We concluded that copper delayed amphibian metamorphosis through changing mRNA expression of Dio3, TRα and TRβ, which suggests that copper might have the endocrine-disrupting effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening of Blood Levels of Mercury, Cadmium, and Copper in Pregnant Women in Dakahlia, Egypt: New Attention to an Old Problem.

PubMed

Motawei, Shimaa M; Gouda, Hossam E

2016-06-01

Heavy metals toxicity is a prevalent health problem particularly in developing countries. Mercury and cadmium are toxic elements that have no physiologic functions in human body. They should not be present in the human body by any concentration. Copper, on the other hand, is one of the elements that are essential for normal cell functions and a deficiency as well as an excess of which can cause adverse health effects. To test blood levels of mercury, cadmium, and copper in pregnant women in Dakahlia, Egypt. Using atomic absorption spectrophotometry, blood levels of cadmium, mercury, and copper were measured in 150 pregnant women attending to the antenatal care in Mansoura University Hospital in Dakahlia governorate, Egypt. The mean ± SD of blood mercury, cadmium, and copper levels were found to be far from their levels in the population surveys carried in developed countries like United States of America (USA) and Canada. Heavy metal intoxication and accumulation is a major health hazard. Developing countries, including Egypt, still lack many of the regulatory policies and legislations to control sources of pollution exposure. This should be dealt with in order to solve this problem and limit its health consequences.

Bioaccumulation of metals in plants, arthropods, and mice at a seasonal wetland.

PubMed

Torres, K C; Johnson, M L

2001-11-01

Concentrations of arsenic, cadmium, copper, lead, and nickel were measured in soils, house mice (Mus musculus), and the main food items of this omnivorous mouse to examine the occurrence of these metals in selected components of a seasonal wetland. Soil concentrations of copper, lead, and (in some areas) nickel were elevated, but extractable soil concentrations indicated low bioavailability of metals. Levels of most metals in mice and composited arthropods were consistent with reference site concentrations from other studies. However, copper was found to be particularly mobile within the local ecosystem and accumulated in house mouse carcasses and composited arthropods at substantial levels. Metal residues in Scirpus robustus (alkali bulrush) roots exceeded those in seeds, consistent with patterns of bioaccumulation commonly observed in plants. Uptake and bioaccumulation factors for S. robustus seeds and roots, arthropods, and mouse carcasses and livers are reported. Concentrations of lead and nickel in S. robustus roots exhibited significant linear relationships with levels in soils. Copper levels in S. robustus seeds varied significantly with those in house mouse livers, suggesting that trophic transfer of copper from this food source to mice occurred. However, other spatial patterns of bioaccumulation in S. robustus and house mice relative to soil/seed concentrations were absent. Metal levels in house mice bore no relation to body weight or estimated age.

The Variations of Glycolysis and TCA Cycle Intermediate Levels Grown in Iron and Copper Mediums of Trichoderma harzianum.

PubMed

Tavsan, Zehra; Ayar Kayali, Hulya

2015-05-01

The efficiency of optimal metabolic function by microorganism depends on various parameters, especially essential metal supplementation. In the present study, the effects of iron and copper metals on metabolism were investigated by determination of glycolysis and tricarboxylic acid (TCA) cycle metabolites' levels with respect to the metal concentrations and incubation period in Trichoderma harzianum. The pyruvate and citrate levels of T. harzianum increased up to 15 mg/L of copper via redirection of carbon flux though glycolysis by suppression of pentose phosphate pathway (PPP). However, the α-ketoglutarate levels decreased at concentration higher than 5 mg/L of copper to overcome damage of oxidative stress. The fumarate levels correlated with the α-ketoglutarate levels because of substrate limitation. Besides, in T. harzianum cells grown in various concentrations of iron-containing medium, the intracellular pyruvate, citrate, and α-ketoglutarate levels showed positive correlation with iron concentration due to modifying of expression of glycolysis and TCA cycle enzymes via a mechanism involving cofactor or allosteric regulation. However, as a result of consuming of prior substrates required for fumarate production, its levels rose up to 10 mg/L.

Response to copper of Acidithiobacillus ferrooxidans ATCC 23270 grown in elemental sulfur.

PubMed

Almárcegui, Rodrigo J; Navarro, Claudio A; Paradela, Alberto; Albar, Juan Pablo; von Bernath, Diego; Jerez, Carlos A

2014-11-01

The response of Acidithiobacillus ferrooxidans ATCC 23270 to copper was analyzed in sulfur-grown cells by using quantitative proteomics. Forty-seven proteins showed altered levels in cells grown in the presence of 50 mM copper sulfate. Of these proteins, 24 were up-regulated and 23 down-regulated. As seen before in ferrous iron-grown cells, there was a notorious up-regulation of RND-type Cus systems and different RND-type efflux pumps, indicating that these proteins are very important in copper resistance. Copper also triggered the down-regulation of the major outer membrane porin of A. ferrooxidans in sulfur-grown bacteria, suggesting they respond to the metal by decreasing the influx of cations into the cell. On the contrary, copper in sulfur-grown cells caused an overexpression of putative TadA and TadB proteins known to be essential for biofilm formation in bacteria. Surprisingly, sulfur-grown microorganisms showed increased levels of proteins related with energy generation (rus and petII operons) in the presence of copper. Although rus operon is overexpressed mainly in cells grown in ferrous iron, the up-regulation of rusticyanin in sulfur indicates a possible role for this protein in copper resistance as well. Finally, copper response in A. ferrooxidans appears to be influenced by the substrate being oxidized by the microorganism. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Lipid peroxidation and antioxidant status in workers exposed to PCDD/Fs of metal recovery plants.

PubMed

Chen, Hsiu-Ling; Hsu, Ching-Yi; Hung, Dong-Zong; Hu, Miao-Lin

2006-12-15

Secondary copper smelters, which primarily utilize the waste materials that contain organic impurities, and the zinc recovery plant, which handles mostly fly ash and slag from the iron and steel industry, are major emission sources of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in Taiwan. In this study, we compared the levels of erythrocyte glutathione (GSH), erythrocyte superoxide dismutase (SOD) and plasma malondialdehyde (MDA) in workers at a secondary copper smelting plant and a zinc recovery plant who may have been exposed to PCDD/Fs. Though the PCDD/F levels were higher in workers of zinc recovery plant than those of secondary copper smelting plant, no significant difference was found for serum PCDD/F levels between the two kinds of plants. We observed a significant difference in plasma MDA levels between workers at the zinc recovery plant (2.54 microM) and those at the copper smelting plant (1.79 microM). There was and a significant positive correlation between plasma MDA levels and the PCDD/Fs levels. In addition, we observed that the MDA levels were not affected by smoking and exercise status. Therefore, the data suggest that the MDA levels of the metal recovery workers are influenced by their PCDD/F exposure. The erythrocyte SOD activity in workers from the zinc recovery plant was marginally higher than that from the secondary copper plant (196 vs. 146 units/ml, p<0.06). In both plants, large variations in the MDA and SOD levels were found, especially in the high-PCDD/Fs-exposure group, which may be attributed, at least partially, to the differences in smoking status and the number of cigarettes smoked. Overall, our results indicate a higher oxidative stress in workers of the zinc recovery plant than in workers of the secondary copper smelting plant in Taiwan.

Distinctive Menkes disease variant with occipital horns: Delineation of natural history and clinical phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Proud, V.K.; Mussell, H.G.; Percy, A.K.

1996-10-02

To delineate further the clinical spectrum of Menkes disease, an X-linked recessive disorder of copper transport, we studied 4 related males, ranging in age from 4-38 years, with a unique phenotype that combines manifestations of classical and mild Menkes disease and occipital horn syndrome (OHS). The propositus, an 18-year-old man, was evaluated following an intracerebral hemorrhage at age 15 years and was noted to have marked hypotonia, motor delay with mental retardation, bladder diverticula, failure to thrive, and diarrhea from infancy; seizures from age 3 years; and abnormal hair (pili torti) and face, cutis laxa, and multiple joint dislocations. Radiographicmore » abnormalities included occipital exostoses, tortuous cerebral blood vessels with multiple branch occlusions, and hammer-shaped clavicles. Biochemical studies demonstrated reduced copper and ceruloplasmin levels in serum, and abnormal plasma catecholamine ratios. We reported previously the molecular defect in this family, a splice-site mutation that predicts formation of approximately 20% of the normal Menkes gene product. Here, we detail the clinical course and physical features and radiographic findings in these 4 individuals, and compare their phenotype with classical and mild Menkes and OHS. Unusual Menkes disease variants such as this may escape recognition due to anomalies that appear inconsistent with the diagnosis, particularly prolonged survival and later onset of seizures. Males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport. 28 refs., 8 figs.« less

The role of essential trace elements in embryonic and fetal development in livestock.

PubMed

Hostetler, Chris E; Kincaid, Ron L; Mirando, Mark A

2003-09-01

This review addresses the concept that essential trace minerals play a vital role in many enzymatic and metabolic pathways that are critical for conceptus development during pregnancy in livestock species. The conceptus relies entirely on the maternal system for a sufficient supply of trace minerals and other nutrients needed for normal development. If this supply is inadequate, growth and/or health of the conceptus can be affected adversely, and many of these effects carry over into the neonatal period. Information, accumulated in our laboratory and presented herein, indicates that zinc, copper and manganese are among the trace minerals that have the greatest impact on reproduction. For example, levels of zinc, copper and manganese were several fold greater in the conceptus than in other reproductive tissues, indicating that the conceptus preferentially accumulates these minerals, an action that may be important for conceptus development, growth and survival. Moreover, some recent results indicate that increasing the biological availability of zinc, copper and manganese, by attachment to short peptide chains (i.e., proteinated trace minerals) can enhance reproductive performance of swine. Mineral concentrations in conceptuses from female pigs consuming proteinated trace minerals were greater than those from females that consumed only inorganic mineral salts. Elucidating the mechanisms whereby conceptus development and survival are enhanced by essential trace minerals may lead to development of specific feeding programs to increase the number and health of offspring at parturition, thereby allowing for further improvements in production efficiency in animal agriculture.

Expression analysis of metallothioneins and mineral contents in tomato (Lycopersicon esculentum) under heavy metal stress.

PubMed

Kısa, Dursun; Öztürk, Lokman; Doker, Serhat; Gökçe, İsa

2017-04-01

Heavy metals are considered to be the most important pollutants in the contamination of soils; they adversely affect plant growth and development and cause some physiological and molecular changes. The contamination of agricultural soils by heavy metals has changed the mineral element content of vegetables. Plant metallothioneins (MTs) are thought to have the functional role in heavy metal homeostasis, and they are used as the biomarkers for evaluating environmental pollution. We aimed to evaluate the expression of MT isoforms (MT1, 2, 3 and 4) and some mineral element composition of tomato roots, leaves and fruits exposed to copper and lead. Heavy metal applications increased MT1 and MT2 gene expressions compared to the control in the tissues of tomato. The highest level of MT1 and MT2 transcripts was found in roots and leaves, respectively. The expression of MT3 is induced in roots, leaves and fruits except for Pb treatment in roots. MT4 expression increased in fruits; however, other tissues did not show a clear change. Our results indicated that Cu content was higher than Pb in all tissues of tomato. The lower doses of Cu (10 ppm) increased the content of Mg, Fe, Ca and Mn in roots. Pb generally increased the level of minerals in leaves and fruits, but it decreased Mg, Mn and Fe contents in roots. Both heavy metals not only moved to aerial parts but also caused alterations to mineral element levels. These results show that MT transcripts are regulated by Cu and Pb, and expression pattern changes to MT isoforms and tissue types. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Experimenting with a Visible Copper-Aluminum Displacement Reaction in Agar Gel and Observing Copper Crystal Growth Patterns to Engage Student Interest and Inquiry

ERIC Educational Resources Information Center

Xu, Xinhua; Wu, Meifen; Wang, Xiaogang; Yang, Yangyiwei; Shi, Xiang; Wang, Guoping

2016-01-01

The reaction process of copper-aluminum displacement in agar gel was observed at the microscopic level with a stereomicroscope; pine-like branches of copper crystals growing from aluminum surface into gel at a constant rate were observed. Students were asked to make hypotheses on the pattern formation and design new research approaches to prove…

Phytostabilization potential of evening primrose (Oenothera glazioviana) for copper-contaminated sites.

PubMed

Guo, Pan; Wang, Ting; Liu, Yanli; Xia, Yan; Wang, Guiping; Shen, Zhenguo; Chen, Yahua

2014-01-01

A field investigation, field experiment, and hydroponic experiment were conducted to evaluate feasibility of using Oenothera glazioviana for phytostabilization of copper-contaminated soil. In semiarid mine tailings in Tongling, Anhui, China, O. glazioviana, a copper excluder, was a dominant species in the community, with a low bioaccumulation factor, the lowest copper translocation factor, and the lowest copper content in seed (8 mg kg(-1)). When O. glazioviana was planted in copper-polluted farmland soil in Nanjing, Jiangsu, China, its growth and development improved and the level of γ-linolenic acid in seeds reached 17.1%, compared with 8.73% in mine tailings. A hydroponic study showed that O. glazioviana had high tolerance to copper, low upward transportation capacity of copper, and a high γ-linolenic acid content. Therefore, it has great potential for the phytostabilization of copper-contaminated soils and a high commercial value without risk to human health.

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases.

PubMed

Bhattacharjee, Ashima; Chakraborty, Kaustav; Shukla, Aditya

2017-10-18

Copper is a trace element essential for almost all living organisms. But the level of intracellular copper needs to be tightly regulated. Dysregulation of cellular copper homeostasis leading to various diseases demonstrates the importance of this tight regulation. Copper homeostasis is regulated not only within the cell but also within individual intracellular compartments. Inactivation of export machinery results in excess copper being redistributed into various intracellular organelles. Recent evidence suggests the involvement of glutathione in playing an important role in regulating copper entry and intracellular copper homeostasis. Therefore interplay of both homeostases might play an important role within the cell. Similar to copper, glutathione balance is tightly regulated within individual cellular compartments. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis. On the one hand, interplay of glutathione and copper homeostasis performs an important role in normal physiological processes, for example neuronal differentiation. On the other hand, perturbation of the interplay might play a key role in the pathogenesis of copper homeostasis disorders.

Gastrointestinal uptake and distribution of copper in rainbow trout.

PubMed

Clearwater, S J; Baskin, S J; Wood, C M; McDonald, D G

2000-08-01

A single dose of radioactive copper ((64)Cu or new Cu) was infused into the stomach of rainbow trout (Oncorhynchus mykiss) to model dietary copper (Cu) uptake under conditions of a normal nutritional dose and optimum environmental temperature (16 degrees C, 0.117 microg Cu g(-)(1 )body mass). The distribution of new Cu to the gut and internal organs occurred in two phases: rapid uptake by the gut tissues (almost complete by 24 h post-infusion) followed by slower uptake by the internal organs. By 72 h, 60 % of the dose had been excreted, 19 % was still retained in the gut tissue, 10 % remained in the lumen and 12 % had been absorbed across the gut and partitioned amongst the internal organs. A reduction in water temperature of 10 degrees C (to 6 degrees C) significantly retarded components of new Cu distribution (movement of the bolus along the gut and excretion); nonetheless, by 72 h, the fraction absorbed by all the internal organs was similar to that at 16 degrees C. An increase in water temperature of 3 degrees C (to 19 degrees C) caused a pronounced increase in internal organ uptake by 24 h to approximately double the uptake occurring at 16 degrees C. The uptake of new Cu by the gut tissue had a low temperature coefficient (Q(10)<1) consistent with simple diffusion, while the temperature coefficient for transfer of new Cu from gut tissue to the internal organs was high (Q(10)>2), consistent with facilitated transport. Internally, the liver and gall bladder (including bile) were the target organs for dietary Cu partitioning since they were the only organs that concentrated new Cu from the plasma. Individual tissues differed in terms of the exchange of their background Cu pools with new Cu. The background Cu in the walls of the gastrointestinal tract (excluding stomach) exchanged 45-94 % with new Cu from the gut lumen, while tissues such as the stomach, gills, kidney, carcass and fat had 5-7 % exchangeable background Cu. The liver, heart, spleen, ovary, bile and plasma had only 0.2-0.8 % exchangeable background Cu. The gastrointestinal tissues appear to act as a homeostatic organ, regulating the absorption of nutritional (non-toxic) doses of Cu (0. 117 microg g(-)(1 )body mass day(-)(1)) by the internal organs. Within the dose range we used and at optimal temperature (16 degrees C), the new Cu content of the gut tissues fluctuated, but absorption of new Cu by the internal organs remained relatively constant. For example, predosing the fish with non-radioactive Cu caused new Cu absorption by the gut tissues to double and decreased new Cu excretion from 38 to 1.5 %, but had no effect on new Cu uptake by the internal organs. Feeding fish after application of the normal liquid dose of new Cu also had no effect on new Cu uptake by the internal organs, even though the presence of food in the digestive tract reduced the binding of new Cu to the gut tissues and assisted with the excretion of new Cu. The gut was therefore able to regulate new Cu internalization at this dosage. Higher new Cu doses (10, 100 and 1000 times the normal dose), however, evoked regurgitation and increased new Cu excretion within 4 h of application but did not elevate new Cu levels in gut tissue beyond a threshold of approximately 40 microg of new Cu. Only at the highest dose (1000 times the normal dose, 192 microg g(-)(1 )body mass), equivalent to toxic concentrations in the daily diet (7000 microg Cu g(-)(1 )dry mass food), was the buffering capacity of the gut overwhelmed, resulting in an increase in internal new Cu uptake.

Mercury and other Mining-Related Contaminants in Ospreys along the Upper Clark Fork River, MT

NASA Astrophysics Data System (ADS)

Langner, H.; Domenech, R.; Greene, E.; Staats, M. F.

2010-12-01

Osprey (Pandion haliaetus) are widely recognized as bio-indicators of the health of aquatic ecosystems. Until the time of fledging, nestlings feed exclusively on fish caught within a few kilometers of the nest. Therefore, tissues of these young birds may reflect the level of contamination of local fish and more generally, the contamination status of the aquatic ecosystem they inhabit. Nests can often be accessed with a boom truck and obtaining small blood samples from the flightless chicks is fairly noninvasive. Ospreys are nesting along the Upper Clark Fork River, Montana, which is heavily contaminated with wastes left from a century of copper and precious metals mining. We have been monitoring the levels of priority pollutants (arsenic, cadmium, lead, copper, zinc, mercury and selenium) in Osprey chicks along a 250 km section of the river for four years. Objectives are to establish current contaminant status, pinpoint pollution hotspots, and assess the success of restoration efforts. Our results suggest that of highest concern may be the bioaccumulation of mercury with blood levels of up to 0.7 mg/L in the growing chicks. These concentrations are expected to increase many fold upon fledging as feather growth stops, which acts as the major sink for mercury. Interestingly, we found mercury levels increased in downstream direction, in contrast to concentrations of other pollutants. Reasons may be the different origin of mercury versus other contaminants and the distribution of wetlands where mercury can be transformed into highly bioavailable methylmercury. Blood levels of selenium are also elevated throughout the Upper Clark Fork River drainage. We discuss the implications for restoration and remediation of the Clark Fork River.

Evaluation of some heavy metals residues in batteries and deep litter rearing systems in Japanese quail meat and offal in Egypt

PubMed Central

Ahmed, Ali M.; Hamed, Dalia M.; Elsharawy, Nagwa T.

2017-01-01

Aim: The main objectives of this study were for comparing the effect of batteries and deep litter rearing systems of domesticated Japanese quail, Coturnix coturnix japonica, on the concentration levels of cadmium, copper, lead, and zinc from the quail meat and offal in Ismailia, Egypt. Materials and Methods: A total of 40 quail meat and their offal samples were randomly collected from two main quail rearing systems: Battery (Group I) and deep litter system (Group II) for determination of concentration levels of cadmium, copper, lead, and zinc. In addition, 80 water and feed samples were randomly collected from water and feeders of both systems in the Food Hygiene Laboratory, Faculty of Veterinary Medicine, Suez Canal University for heavy metals determination. Results: The mean concentration levels of cadmium, copper, lead, and zinc in Group I were 0.010, 0.027, 1.137, and 0.516 ppm and for Group II were 0.093, 0.832, 0.601, and 1.651 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail feed in Group I were 1.114, 1.606, 5.822, and 35.11 ppm and for Group II were 3.010, 2.576, 5.852, and 23.616 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail meat for Group I were 0.058, 5.902, 10.244, and 290 ppm and for Group II were 0.086, 6.092, 0.136, and 1.280 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc for liver samples in Group I were 0.15, 8.32, 1.05, and 3.41 ppm and for Group II were 0.13, 8.88, 0.95, and 4.21 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in kidney samples for the Group I were 0.24, 4.21, 1.96, and 4.03 ppm and for Group II were 0.20, 5.00, 1.56, and 3.78 ppm, respectively. Kidney had the highest concentration levels of heavy metals followed by liver then muscles. The highest concentration levels of copper were observed in liver samples. The order of the levels of these trace elements obtained from the four different quail organs is Ca > Pb > Zn > Cu. Lead and cadmium concentration levels in quail meat samples were exceeded the Egyptian standardization limits and suggesting a health threat from lead and cadmium to the quail consumers. Conclusion: Battery rearing system is more hygienic than deep litter system from the point of heavy metals pollution of water and feeds of quail. Feed samples from battery system had means concentration levels of lead not significantly higher (p>0.05) than those samples from deep litter system. Meanwhile, water samples from battery system had means concentration levels of cadmium, copper, and zinc significantly higher (p>0.05) than those samples from deep litter system. Quail may carry health risks to consumers. PMID:28344413

Evaluation of some heavy metals residues in batteries and deep litter rearing systems in Japanese quail meat and offal in Egypt.

PubMed

Ahmed, Ali M; Hamed, Dalia M; Elsharawy, Nagwa T

2017-02-01

The main objectives of this study were for comparing the effect of batteries and deep litter rearing systems of domesticated Japanese quail, Coturnix coturnix japonica , on the concentration levels of cadmium, copper, lead, and zinc from the quail meat and offal in Ismailia, Egypt. A total of 40 quail meat and their offal samples were randomly collected from two main quail rearing systems: Battery (Group I) and deep litter system (Group II) for determination of concentration levels of cadmium, copper, lead, and zinc. In addition, 80 water and feed samples were randomly collected from water and feeders of both systems in the Food Hygiene Laboratory, Faculty of Veterinary Medicine, Suez Canal University for heavy metals determination. The mean concentration levels of cadmium, copper, lead, and zinc in Group I were 0.010, 0.027, 1.137, and 0.516 ppm and for Group II were 0.093, 0.832, 0.601, and 1.651 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail feed in Group I were 1.114, 1.606, 5.822, and 35.11 ppm and for Group II were 3.010, 2.576, 5.852, and 23.616 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail meat for Group I were 0.058, 5.902, 10.244, and 290 ppm and for Group II were 0.086, 6.092, 0.136, and 1.280 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc for liver samples in Group I were 0.15, 8.32, 1.05, and 3.41 ppm and for Group II were 0.13, 8.88, 0.95, and 4.21 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in kidney samples for the Group I were 0.24, 4.21, 1.96, and 4.03 ppm and for Group II were 0.20, 5.00, 1.56, and 3.78 ppm, respectively. Kidney had the highest concentration levels of heavy metals followed by liver then muscles. The highest concentration levels of copper were observed in liver samples. The order of the levels of these trace elements obtained from the four different quail organs is Ca > Pb > Zn > Cu. Lead and cadmium concentration levels in quail meat samples were exceeded the Egyptian standardization limits and suggesting a health threat from lead and cadmium to the quail consumers. Battery rearing system is more hygienic than deep litter system from the point of heavy metals pollution of water and feeds of quail. Feed samples from battery system had means concentration levels of lead not significantly higher (p>0.05) than those samples from deep litter system. Meanwhile, water samples from battery system had means concentration levels of cadmium, copper, and zinc significantly higher (p>0.05) than those samples from deep litter system. Quail may carry health risks to consumers.

LEAD AND COPPER RESEARCH UPDATE: RECENT AND FUTURE AREAS OF WORK

EPA Science Inventory

Although the Lead and Copper Rule has been in place for over 10 years, many drinking water systems still have difficulty in meeting the lead and copper action levels. Some water quality conditions remain either difficult to treat or changes brought about by treatment changes dir...

A REVIEW OF ACID COPPER PLATING BATH LIFE EXTENSION AND COPPER RECOVERY FROM ACID COPPER BATHS

EPA Science Inventory

Large quantities of hazardous waste, most in aqueous solution or sludges, are being produced at numerous metal plating and processing facilities in the U.S. Regulatory pressures, future liability, and limited landfill space have driven the cost of metal waste disposal to level...

Control of New Copper Corrosion in High-Alkalinity Drinking Water using Orthophosphate - article

EPA Science Inventory

Research and field experience have shown that high-alkalinity waters can be associated with elevated copper levels in drinking water. The objective of this study was to document the application of orthophosphate to the distribution system of a building with a copper problem asso...

Biochemical changes in black oat (avena strigosa schreb) cultivated in vineyard soils contaminated with copper.

PubMed

Girotto, Eduardo; Ceretta, Carlos A; Rossato, Liana V; Farias, Julia G; Brunetto, Gustavo; Miotto, Alcione; Tiecher, Tadeu L; de Conti, Lessandro; Lourenzi, Cledimar R; Schmatz, Roberta; Giachini, Admir; Nicoloso, Fernando T

2016-06-01

Soils used for the cultivation of grapes generally have a long history of copper (Cu) based fungicide applications. As a result, these soils can accumulate Cu at levels that are capable of causing toxicity in plants that co-inhabit the vineyards. The aim of the present study was to evaluate growth parameters and oxidative stress in black oat plants grown in vineyard soils contaminated with high levels of Cu. Soil samples were collected from the Serra Gaúcha and Campanha Gaúcha regions, which are the main wine producing regions in the state of Rio Grande do Sul, in southern Brazil. Experiments were conducted in a greenhouse in 2009, with soils containing Cu concentrations from 2.2 to 328.7 mg kg(-1). Evaluated parameters included plant root and shoot dry matter, Cu concentration in the plant's tissues, and enzymatic and non-enzymatic biochemical parameters related to oxidative stress in the shoots of plants harvested 15 and 40 days after emergence. The Cu absorbed by plants predominantly accumulated in the roots, with little to no translocation to the shoots. Even so, oat plants showed symptoms of toxicity when grown in soils containing high Cu concentrations. The enzymatic and non-enzymatic antioxidant systems of oat plants were unable to reverse the imposed oxidative stress conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effect of an Extract from Aronia melanocarpa L. Berries on the Body Status of Zinc and Copper under Chronic Exposure to Cadmium: An In Vivo Experimental Study

PubMed Central

Borowska, Sylwia; Brzóska, Małgorzata M.; Gałażyn-Sidorczuk, Małgorzata; Rogalska, Joanna

2017-01-01

In an experimental model of low-level and moderate environmental human exposure to cadmium (Cd), it was investigated whether the consumption of a polyphenol-rich Aronia melanocarpa L. berries (chokeberries) extract (AE) may influence the body status of zinc (Zn) and copper (Cu). The bioelements’ apparent absorption, body retention, serum and tissue concentrations, total pool in internal organs, excretion, and the degree of binding to metallothionein were evaluated in female rats administered 0.1% aqueous AE or/and Cd in their diet (1 and 5 mg/kg) for 3–24 months. The consumption of AE alone had no influence on the body status of Zn and Cu. The extract administration at both levels of Cd treatment significantly (completely or partially) protected against most of the changes in the metabolism of Zn and Cu caused by this xenobiotic; however, it increased or decreased some of the Cd-unchanged indices of their body status. Based on the findings, it seems that rational amounts of chokeberry products may be included in the daily diet without the risk of destroying Zn and Cu metabolisms; however, their potential prophylactic use under exposure to Cd needs further study to exclude any unfavourable impact of these essential elements on the metabolism. PMID:29257101

Investigation of the copper contents in vineyard soil, grape must and wine and the relationship among them in the Huaizhuo Basin Region, China: A preliminary study.

PubMed

Sun, Xiangyu; Ma, Tingting; Yu, Jing; Huang, Weidong; Fang, Yulin; Zhan, Jicheng

2018-02-15

The copper contents in vineyard soil, grape must and wine and the relationship among them in the Huaizhuo Basin Region, China, were investigated. The results showed that the copper pollution status in vineyard soils, grapes and wines in the investigated area in China is under control, with only 4 surface soil (0-20cm) samples over maximum residue limits (MRL) and no grape or wine samples over MRL. Different vineyards, grape varieties, vine ages, and training systems all significantly influenced the copper contents in the vineyard soils, grape and wines. Additionally, the copper levels in the vineyard soils, grapes and wines all had some correlation. In wine samples, the copper contents ranged from 0.52 to 663μg/L, which is only approximately one percent the level found in grapes and one ten-thousandth that found in soils. Of the wine samples, red wines showed a significantly higher copper content than white wines, while in the red/white grape and soil samples, no significant differences were observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes in Water Regime.

PubMed

Li, Jing; Liu, Yu-Rong; Cui, Li-Juan; Hu, Hang-Wei; Wang, Jun-Tao; He, Ji-Zheng

2017-11-01

Increasing efforts have been devoted to exploring the impact of environmental stresses on soil bacterial communities, but the work on the archaeal community is seldom. Here, we constructed microcosm experiments to investigate the responses of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution. Ten DW cycles were exerted on the two soils with different copper levels, followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon index) in the high copper-level treatments increased over the incubation period, and archaeal community structure changed remarkably as revealed by the non-metric multidimensional scaling ordinations. In both soils, copper pollution altered the response of dominant operational taxonomic units (OTUs) to the DW disturbance. Throughout the incubation and recovery period, the resistance of archaeal abundance to the DW disturbance was higher in the copper-polluted soils than soils without pollution. Taken together, copper pollution altered the response of soil archaeal diversity and community composition to the DW disturbance and increased the resistance of the archaeal abundance. These findings have important implications for understanding soil microbial responses to ongoing environmental change.

The effects of copper fining on the wine content in sulfur off-odors and on their evolution during accelerated anoxic storage.

PubMed

Vela, Eduardo; Hernández-Orte, Purificación; Franco-Luesma, Ernesto; Ferreira, Vicente

2017-09-15

Three different red wines with reductive character have been treated with two different doses of copper sulfate (0.06 and 0.5mg/L) and with a commercial copper-containing product at the recommended dose (0.6mg/L). Wines were in contact with copper one week, centrifuged and stored at 50°C in strict anoxia for 2weeks (up to 7 in one case). Brine-releasable (BR-) and free fractions of Volatile Sulfur Compounds were determined throughout the process. Relevant increases of BR-H 2 S suggest that those wines contained other H 2 S precursors non-detectable by the brine dilution method. Copper treatments had two major effects: 1) immediate decrease the levels of free H 2 S and methanethiol (MeSH); 2) slow the rate at which free H 2 S (not MeSH) increases during anoxic storage. After 7weeks of anoxia levels of free H 2 S and MeSH were high and similar regardless of the copper treatment. Higher copper doses could induce the accumulation of BR-H 2 S. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluorescence Lifetime Imaging of Physiological Free Cu(II) Levels in Live Cells with a Cu(II)-Selective Carbonic Anhydrase-Based Biosensor

PubMed Central

McCranor, Bryan J.; Szmacinski, Henryk; Zeng, Hui Hui; Stoddard, A.K.; Hurst, Tamiika; Fierke, Carol A.; Lakowicz, J.R.

2014-01-01

Copper is a required trace element that plays key roles in a number of human enzymes, such that copper deficiency or genetic defects in copper transport lead to serious or fatal disease. Rae, et al., had famously predicted that free copper ion levels in the cell cytoplasm were extremely low, typically too low to be observable. We recently developed a variant of human apocarbonic anhydrase II for sensing metal ions that exhibits 25-fold better selectivity for Cu(II) over Zn(II) than the wild type protein, enabling us to accurately measure Cu(II) in the presence of ordinary cellular (picomolar) concentrations of free zinc. We inserted a fluorescent labeled Cu(II)-specific variant of human apocarbonic anhydrase into PC-12 cells and found that the levels are indeed extremely low (in the femtomolar range). We imaged the free Cu(II) levels in living cells by means of frequency-domain fluorescence lifetime microscopy. Implications of this finding are discussed. PMID:24671220

Regulation of extracellular copper-binding proteins in copper-resistant and copper-sensitive mutants of Vibrio alginolyticus.

PubMed Central

Harwood, V J; Gordon, A S

1994-01-01

Extracellular proteins of wild-type Vibrio alginolyticus were compared with those of copper-resistant and copper-sensitive mutants. One copper-resistant mutant (Cu40B3) constitutively produced an extracellular protein with the same apparent molecular mass (21 kDa) and chromatographic behavior as copper-binding protein (CuBP), a copper-induced supernatant protein which has been implicated in copper detoxification in wild-type V. alginolyticus. Copper-sensitive V. alginolyticus mutants displayed a range of alterations in supernatant protein profiles. CuBP was not detected in supernatants of one copper-sensitive mutant after cultures had been stressed with 50 microM copper. Increased resistance to copper was not induced by preincubation with subinhibitory levels of copper in the wild type or in the copper-resistant mutant Cu40B3. Copper-resistant mutants maintained the ability to grow on copper-amended agar after 10 or more subcultures on nonselective agar, demonstrating the stability of the phenotype. A derivative of Cu40B3 with wild-type sensitivity to copper which no longer constitutively expressed CuBP was isolated. The simultaneous loss of both constitutive CuBP production and copper resistance in Cu40B3 indicates that constitutive CuBP production is necessary for copper resistance in this mutant. These data support the hypothesis that the extracellular, ca. 20-kDa protein(s) of V. alginolyticus is an important factor in survival and growth of the organism at elevated copper concentrations. The range of phenotypes observed in copper-resistant and copper-sensitive V. alginolyticus indicate that altered sensitivity to copper was mediated by a variety of physiological changes. Images PMID:8031076

Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins▿†

PubMed Central

Reeder, Nancy L.; Kaplan, Jerry; Xu, Jun; Youngquist, R. Scott; Wallace, Jared; Hu, Ping; Juhlin, Kenton D.; Schwartz, James R.; Grant, Raymond A.; Fieno, Angela; Nemeth, Suzanne; Reichling, Tim; Tiesman, Jay P.; Mills, Tim; Steinke, Mark; Wang, Shuo L.; Saunders, Charles W.

2011-01-01

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal. PMID:21947398

Metabolism and tissue distribution of trace elements in broiler chickens' fed diets containing deficient and plethoric levels of copper, manganese, and zinc.

PubMed

Mondal, Sovik; Haldar, Sudipto; Saha, Pinaki; Ghosh, Tapan Kumar

2010-11-01

Supplementation of broiler diets with copper, manganese, and zinc at levels higher than that stipulated by the National Research Council 1994 reportedly improved live weight, feed conversion, and cured leg abnormality supposedly caused by inadequate intake of Mn and Zn. The objective of the study was to ascertain the effects of plethoric supplementation of copper (Cu), manganese (Mn), and zinc (Zn) on performance and metabolic responses in broiler chickens. The study also aimed to discriminate the responses of the birds when the mineral elements were supplemented either in an inorganic or in an organic form. Cobb 400 broiler chickens (1-day old, n = 300) were assigned to three dietary treatments each containing nine replicates with ten birds for 39 days. The treatments included a control in which the diet was devoid of supplemental trace elements and treatments supplemented with an inorganic trace element premix (ITM) and supplemented with a combination of the inorganic and an organic trace element premix (OTM). The ITM contained (per kilogram) copper, 15 g; iron, 90 g; manganese, 90 g; zinc, 80 g (all as sulfated salts); iodine (as potassium iodide), 2 g; and selenium (as sodium selenite), 0.3 g. The OTM on the other hand, contained copper, 2.5 g; iron, 15 g; manganese, 15 g; zinc, 13.33 g; and chromium, 0.226 g (all as protein chelates). Plethoric supplementation of trace elements improved live weight gain and feed/gain ratio (p < 0.05). Leg abnormality developed in the 16% of the control group of birds but not in the supplemented group. Metabolizability of dry matter, organic matter, and protein was higher (p < 0.01) in the ITM and OTM groups. Excretion of Cu, Fe, and Zn decreased (p < 0.1) due to supplementation of the trace elements leading to increased apparent absorption of the said mineral elements (p < 0.01). Concentration of the concerned trace elements in serum, liver, and composite muscle samples was higher (p < 0.05) in the ITM and OTM dietary groups indicating an increased deposition of the said mineral elements due to supplementation. Although the study revealed subtle difference between the inorganic and organic mineral premixes with regards to the parameters mentioned above, it became apparent that it is possible to reduce excretion of these trace elements by a judicious escalation in the level of supplementation. The results of the present investigation further revealed that the trace mineral requirement of broiler chickens suggested by the National Research Council may not be optimum to support the maximum growth potential of the high yielding strains, and it is reasonable to consider a review of the current NRC recommendations to meet the needs of the modern birds.

[Estimation of mercury in the urine of cigarette smokers].

PubMed

Kulikowska-Karpińska, Elżbieta; Zdanowicz, Magdalena; Gałażyn-Sidorczuk, Małgorzata

Cigarette smoking is one of the most common habits of the modern world. According to a NATPOL PLU study, every third adult Pole is dependent on nicotine. Tobacco smoke contains about 5,000 components, of which over 1,000 are very toxic chemical substances (3,4-benzopyrene, heavy metals, free radicals, hydrogen cyanide, nitrogen oxides and N-nitrosamines). Exposure to tobacco smoke is an example of a complex, with a significant number of interactions. To assess the concentration of copper in the urine of smokers. Based on the results, an attempt was made to determine whether smoking can affect the level of copper in the body. The study involved 170 healthy volunteers, 99 smokers and 71 non-smokers (control group). The age of patients in both groups were in the range of 20-60 years. The mean age for men and women was 41 years. The average length of cigarette smoking was 18 years for women and 21 years for men, and the number of cigarettes smoked 1-40 ⁄ 24. The urine concentrations of Cu were determined by atomic absorption spectrometry (AAS) and serum creatinine kinetic method using a set of BIOLAB. Cu concentration in urine was expressed in mg / g creatinine. Smokers were found to have reduced levels of copper in the urine, depending on sex, age and brand of cigarettes. In male smokers, copper concentration in the urine was dependent on age and time of smoking, whereas among women this relationship was not observed. Cigarette smoking significantly influences the level of copper in the urine. Both female and male smokers showed reduced levels of copper in the urine, which may indicate its increased accumulation in the body. Excessive accumulation of copper is very dangerous since it may exhibit toxic effects towards many organs and systems.

Wide range of metallic and organic contaminants in various tissues of the Antarctic prion, a planktonophagous seabird from the Southern Ocean.

PubMed

Fromant, Aymeric; Carravieri, Alice; Bustamante, Paco; Labadie, Pierre; Budzinski, Hélène; Peluhet, Laurent; Churlaud, Carine; Chastel, Olivier; Cherel, Yves

2016-02-15

Trace elements (n=14) and persistent organic pollutants (POPs, n=30) were measured in blood, liver, kidney, muscle and feathers of 10 Antarctic prions (Pachyptila desolata) from Kerguelen Islands, southern Indian Ocean, in order to assess their concentrations, tissue distribution, and inter-tissue and inter-contaminant relationships. Liver, kidney and feathers presented the highest burdens of arsenic, cadmium and mercury, respectively. Concentrations of cadmium, copper, iron, and zinc correlated in liver and muscle, suggesting that uptake and pathways of metabolism and storage were similar for these elements. The major POPs were 4,4'-DDE, mirex, PCB-153 and PCB-138. The concentrations and tissue distribution patterns of environmental contaminants were overall in accordance with previous results in other seabirds. Conversely, some Antarctic prions showed surprisingly high concentrations of BDE-209. This compound has been rarely observed in seabirds before, and its presence in Antarctic prions could be due to the species feeding habits or to the ingestion of plastic debris. Overall, the study shows that relatively lower trophic level seabirds (zooplankton-eaters) breeding in the remote southern Indian Ocean are exposed to a wide range of environmental contaminants, in particular cadmium, selenium and some emerging-POPs, which merits further toxicological investigations. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a tightly regulated and highly responsive copper-inducible gene expression system and its application to control of flowering time.

PubMed

Saijo, Takanori; Nagasawa, Akitsu

2014-01-01

A newly developed copper-inducible gene expression system overcame the mixed results reported earlier, worked well both in cultured cells and a whole plant, and enabled to control flowering timing. Copper is one of the essential microelements and is readily taken up by plants. However, to date, it has rarely been used to control the expression of genes of interest, probably due to the inefficiency of the gene expression systems. In this study, we successfully developed a copper-inducible gene expression system that is based on the regulation of the yeast metallothionein gene. This system can be applied in the field and regulated at approximately one-hundredth of the rate used for registered copper-based fungicides. In the presence of copper, a translational fusion of the ACE1 transcription factor with the VP16 activation domain (VP16AD) of herpes simplex virus strongly activated transcription of the GFP gene in transgenic Arabidopsis. Interestingly, insertion of the To71 sequence, a 5'-untranslated region of the 130k/180k gene of tomato mosaic virus, upstream of the GFP gene reduced the basal expression of GFP in the absence of copper to almost negligible levels, even in soil-grown plants that were supplemented with ordinary liquid nutrients. Exposure of plants to 100 μM copper resulted in an over 1,000-fold induction ratio at the transcriptional level of GFP. This induction was copper-specific and dose-dependent with rapid and reversible responses. Using this expression system, we also succeeded in regulating floral transition by copper treatment. These results indicate that our newly developed copper-inducible system can accelerate gene functional analysis in model plants and can be used to generate novel agronomic traits in crop species.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarwar, Tarique; Zafaryab, Md; Husain, Mohammed Amir

Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we havemore » shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS. - Highlights: • Pro-oxidant properties of ferulic acid are enhanced in presence of copper. • Ferulic acid causes oxidative DNA damage in lymphocytes as observed by comet assay. • DNA damage was ameliorated by copper chelating agent neocuproine and ROS scavengers. • Endogenous copper is involved in ROS generation causing DNA damage. • Ferulic acid exerts cancer cell specific cytotoxicity as observed by MTT assay.« less

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women

PubMed Central

Choi, Rihwa; Sun, Jiyu; Yoo, Heejin; Kim, Seonwoo; Cho, Yoon Young; Kim, Hye Jeong; Kim, Sun Wook; Chung, Jae Hoon; Oh, Soo-young; Lee, Soo-Youn

2016-01-01

This prospective study sought to investigate serum levels of trace elements (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women (median gestational age at delivery was 39 + 4 weeks and interquartile range was 38 + 4–40 + 1 weeks) were compared with those of 527 general adults and those of previous studies in other ethnic groups. Pregnancy and neonatal outcomes including gestational diabetes, preeclampsia, neonatal birth weight, and congenital abnormalities were assessed. The median serum trace element concentrations of all pregnant women were: cobalt: 0.39 μg/L (interquartile range, IQR 0.29–0.53), copper: 165.0 μg/dL (IQR 144.0–187.0), zinc: 57.0 μg/dL (IQR 50.0–64.0), and selenium: 94.0 μg/L (IQR 87.0–101.0). Serum cobalt and copper concentrations were higher in pregnant women than in the general population, whereas zinc and selenium levels were lower (p < 0.01). Concentrations of all four trace elements varied significantly during the three trimesters (p < 0.05), and seasonal variation was found in copper, zinc, and selenium, but was not observed for cobalt. The prevalence of preeclampsia was significantly lower with high copper (p = 0.03). Trace element levels varied by pregnancy trimester and season, and alteration in copper status during pregnancy might influence pregnancy outcomes such as preeclampsia. PMID:27886083

A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women.

PubMed

Choi, Rihwa; Sun, Jiyu; Yoo, Heejin; Kim, Seonwoo; Cho, Yoon Young; Kim, Hye Jeong; Kim, Sun Wook; Chung, Jae Hoon; Oh, Soo-Young; Lee, Soo-Youn

2016-11-23

This prospective study sought to investigate serum levels of trace elements (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women (median gestational age at delivery was 39 + 4 weeks and interquartile range was 38 + 4-40 + 1 weeks) were compared with those of 527 general adults and those of previous studies in other ethnic groups. Pregnancy and neonatal outcomes including gestational diabetes, preeclampsia, neonatal birth weight, and congenital abnormalities were assessed. The median serum trace element concentrations of all pregnant women were: cobalt: 0.39 μg/L (interquartile range, IQR 0.29-0.53), copper: 165.0 μg/dL (IQR 144.0-187.0), zinc: 57.0 μg/dL (IQR 50.0-64.0), and selenium: 94.0 μg/L (IQR 87.0-101.0). Serum cobalt and copper concentrations were higher in pregnant women than in the general population, whereas zinc and selenium levels were lower ( p < 0.01). Concentrations of all four trace elements varied significantly during the three trimesters ( p < 0.05), and seasonal variation was found in copper, zinc, and selenium, but was not observed for cobalt. The prevalence of preeclampsia was significantly lower with high copper ( p = 0.03). Trace element levels varied by pregnancy trimester and season, and alteration in copper status during pregnancy might influence pregnancy outcomes such as preeclampsia.

Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

NASA Technical Reports Server (NTRS)

Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

1999-01-01

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

Investigation of the interaction of copper(II) oxide and electron beam irradiation crosslinkable polyethylene

NASA Astrophysics Data System (ADS)

Bee, Soo-Tueen; Sin, Lee Tin; Ratnam, C. T.; Haraveen, K. J. S.; Tee, Tiam-Ting; Rahmat, A. R.

2015-10-01

In this study, the effects of electron beam irradiation on the properties of copper(II) oxide when added to low-density polyethylene (LDPE) blends were investigated. It was found that the addition of low loading level of copper(II) oxide (⩽2 phr) to LDPE results in significantly poorer gel content and hot set results. However, the incorporation of higher loading level of copper(II) oxide (⩾3 phr) could slightly increase the degree of crosslinking in all irradiated LDPE composites. This is due to the fact that higher amounts of copper(II) oxide could slightly induce the formation of free radicals in LDPE matrix. Besides, increasing irradiation doses was also found to gradually increase the gel content of LDPE composites by generating higher amounts of free radicals. As a consequence, these higher amounts of free radicals released in the LDPE matrix could significantly increase the degree of crosslinking. The addition of copper(II) oxide could reduce the tensile strength and fracture strain (elongation at break) of LDPE composites because of poorer interfacial adhesion effect between copper(II) oxide particles and LDPE matrix. Meanwhile, increasing irradiation doses on all copper(II) oxide added LDPE composites could marginally increase the tensile strength. In addition, increasing irradiation dose could enhance the thermal stability of LDPE composites by increasing the decomposition temperature. The oxidation induction time (OIT) analysis showed that, because of the crosslinking network in the copper(II) oxide added LDPE composites, oxidation reaction is much delayed.

Trace metal accumulation and fish pathologies in areas affected by mining and metallurgical enterprises in the Kola Region, Russia.

PubMed

Moiseenko, T I; Kudryavtseva, L P

2001-01-01

Throughout the Kola region of Russia there has been a substantial increase of metal concentrations in water, which are related to local discharges from metallurgical and mining industry, transboundary transmissions as well as indirect leaching of elements by acid precipitation. This study presents data on the levels of Ni, Cu, Sr, Al, Zn, Co, Mn, Pb, Cd, Hg in the organs and tissues of fish, and evaluates relationships with water chemistry. Special attention is paid to fish pathologies, whose aetiology is related to the accumulation of metals and the associated changes of the elementary ratios within the organism. Ecotoxicological assessment of the copper nickel, strontium and acidification regimes also is considered in this article. In general we observed a large number of lakes that are heavily contaminated by Ni and Cu. Fish in these lakes contain high concentrations of Ni and Cu and display frequent pathologies, mostly associated with the kidneys. In lakes contaminated with Sr, there also are high Sr levels in fish and pathologies associated with skeletal tissues. Exposure to acidified water appears to increase the transport of metals (including Al, Ni and Cu) into fish and hence the toxic effects.

Biomarker responses of mussels exposed to earthquake disturbances

NASA Astrophysics Data System (ADS)

Chandurvelan, Rathishri; Marsden, Islay D.; Glover, Chris N.; Gaw, Sally

2016-12-01

The green-lipped mussel, Perna canaliculus is recognised as a bioindicator of coastal contamination in New Zealand (NZ). Mussels (shell length 60-80 mm) were collected from three intertidal areas of Canterbury in the South Island of NZ prior to extreme earthquake disturbances on 22nd February 2011, and 9 months later in October 2011. Trace elements, including arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn), were measured in the gills, digestive gland, foot and mantle. Metal levels in tissues were site specific, and mostly unaffected by earthquake disturbances. Physiological biomarkers were negatively affected by earthquake disturbances and mussels from the Port of Lyttelton had higher negative scope for growth post-earthquake. Metallothionein-like protein in the digestive gland correlated with metal content of tissues, as did catalase activity in the gill and lipid peroxidation values for the digestive gland. This research demonstrates that physiological and other biomarkers are effective at detecting the effects of multiple stressors following seismic disturbances.

Metals in lung tissue from autopsy cases in Mexico City residents: comparison of cases from the 1950s and the 1980s.

PubMed Central

Fortoul, T I; Osorio, L S; Tovar, A T; Salazar, D; Castilla, M E; Olaiz-Fernández, G

1996-01-01

In autopsies performed on residents of Mexico City during the 1950s and 1980s (45 males and 24 females and 42 males and 42 females, respectively), concentrations of cadmium, copper, cobalt, nickel, and lead in the lungs were studied by atomic absorption spectrometry. Sharp increases were noted in samples taken in the 1980s compared to those from the 1950s. In samples from both time periods, the concentrations were influenced by gender. Smoking was not associated with higher levels of the metals. Only lead seemed to have a relation with age. The enormous differences by gender in the 1950s could be due to different patterns of exposure. The differences among samples from both periods appear to be associated with the increase of air pollutants in the metropolitan areas of Mexico City during the years under study. These results reinforce the importance of studying lung tissue to monitor air pollution by metals. PMID:8793351

Economic booms and risky sexual behavior: evidence from Zambian copper mining cities.

PubMed

Wilson, Nicholas

2012-12-01

Existing studies suggest that individual and household level economic shocks affect the demand for and supply of risky sex. However, little evidence exists on the effects of an aggregate shock on equilibrium risky sexual behavior. This paper examines the effects of the early twenty-first century copper boom on risky sexual behavior in Zambian copper mining cities. The results suggest that the copper boom substantially reduced rates of transactional sex and multiple partnerships in copper mining cities. These effects were partly concentrated among young adults and copper boom induced in-migration to mining cities appears to have contributed to these reductions. Copyright © 2012. Published by Elsevier B.V.

THE IMPACT OF HEXAMETAPHOSPHATE ON COPPER CORROSION AND RELEASE

EPA Science Inventory

In 1991, U.S. Environmental Protection Agency (U.S. EPA) promulgated the Lead and Copper Rule, which established a copper action level of 1.3 mg/L in a 1-liter, first-draw sample collected from the consumer’s tap (Federal Register, 1991a, 1991b, 1992). The rule was established d...

Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo.

PubMed

Hassan, Iftekhar; Khan, Azmat Ali; Aman, Shazia; Qamar, Wajhul; Ebaid, Hossam; Al-Tamimi, Jameel; Alhazza, Ibrahim M; Rady, Ahmed M

2018-01-26

The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions. The treated cells were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3, LDH and single cell electrophoresis. The study shows that DSF and Cu (II) synergizes the anticancer activity of ITB to a significant extent in a dose-specific way as evidenced by the combinations treated groups. Furthermore, the same treatment strategy was employed in cancer-induced rats in which the combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as compared to ITB alone. However, DSF was more effective than Cu (II) as an adjuvant to the drug. Hence, restrained manipulation of copper level in tumor cells can orchestrate the redox and molecular dispositions inside the cells favoring the induction of apoptosis.

Systems biology approach in Chlamydomonas reveals connections between copper nutrition and multiple metabolic steps.

PubMed

Castruita, Madeli; Casero, David; Karpowicz, Steven J; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I; Yan, Weihong; Cokus, Shawn; Loo, Joseph A; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S

2011-04-01

In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O₂-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper.

Hydrocarbon-fuel/copper combustion chamber liner compatibility, corrosion prevention, and refurbishment

NASA Technical Reports Server (NTRS)

Rosenberg, S. D.; Gage, M. L.; Homer, G. D.; Franklin, J. E.

1991-01-01

An evaluation is made of combustion product/combustion chamber compatibility in the case of a LOX/liquid hydrocarbon booster engine based on copper-alloy thrust chamber which is regeneratively cooled by the fuel. It is found that sulfur impurities in the fuel are the primary causes of copper corrosion, through formation of Cu2S; sulfur levels as low as 1 ppm can result in sufficiently severe copper corrosion to degrade cooling channel performance. This corrosion can be completely eliminated, however, through the incorporation of an electrodeposited gold coating on the copper cooling-channel walls.

Relation of serum γ-glutamyl transferase activity with copper in an adult population.

PubMed

Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

2017-10-26

The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, p<0.001). There was a positive correlation between serum γ-GGT activity and copper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, p<0.001; r=0.230, p=0.010). The results of multiple linear regression analysis showed that serum γ-GGT maintained a significantly positive correlation with copper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

Copper effects on key metabolic enzymes and mitochondrial membrane potential in gills of the estuarine crab Neohelice granulata at different salinities.

PubMed

Lauer, Mariana Machado; de Oliveira, Camila Bento; Yano, Natalia Lie Inocencio; Bianchini, Adalto

2012-11-01

The estuarine crab Neohelice granulata was exposed (96 h) to a sublethal copper concentration under two different physiological conditions (hyperosmoregulating crabs: 2 ppt salinity, 1 mg Cu/L; isosmotic crabs: 30 ppt salinity, 5 mg Cu/L). After exposure, gills (anterior and posterior) were dissected and activities of enzymes involved in glycolysis (hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase), Krebs cycle (citrate synthase), and mitochondrial electron transport chain (cytochrome c oxidase) were analyzed. Membrane potential of mitochondria isolated from anterior and posterior gill cells was also evaluated. In anterior gills of crabs acclimated to 2 ppt salinity, copper exposure inhibited hexokinase, phosphofructokinase, pyruvate kinase, and citrate synthase activity, increased lactate dehydrogenase activity, and reduced the mitochondrial membrane potential. In posterior gills, copper inhibited hexokinase and pyruvate kinase activity, and increased citrate synthase activity. In anterior gills of crabs acclimated to 30 ppt salinity, copper exposure inhibited phosphofructokinase and citrate synthase activity, and increased hexokinase activity. In posterior gills, copper inhibited phosphofructokinase and pyruvate kinase activity, and increased hexokinase and lactate dehydrogenase activity. Copper did not affect cytochrome c oxidase activity in either anterior or posterior gills of crabs acclimated to 2 and 30 ppt salinity. These findings indicate that exposure to a sublethal copper concentration affects the activity of enzymes involved in glycolysis and Krebs cycle, especially in anterior (respiratory) gills of hyperosmoregulating crabs. Changes observed indicate a switch from aerobic to anaerobic metabolism, characterizing a situation of functional hypoxia. In this case, reduced mitochondrial membrane potential would suggest a decrease in ATP production. Although gills of isosmotic crabs were also affected by copper exposure, changes observed suggest no impact in the overall tissue ATP production. Also, findings suggest that copper exposure would stimulate the pentose phosphate pathway to support the antioxidant system requirements. Although N. granulata is very tolerant to copper, acute exposure to this metal can disrupt the energy balance by affecting biochemical systems involved in carbohydrate metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

An Expanding Range of Functions for the Copper Chaperone/Antioxidant Protein Atox1

PubMed Central

Hatori, Yuta

2013-01-01

Abstract Significance: Antioxidant protein 1 (Atox1 in human cells) is a copper chaperone for the copper export pathway with an essential role in cellular copper distribution. In vitro, Atox1 binds and transfers copper to the copper-transporting ATPases, stimulating their catalytic activity. Inactivation of Atox1 in cells inhibits maturation of secreted cuproenzymes as well as copper export from cells. Recent Advances: Accumulating data suggest that cellular functions of Atox1 are not limited to its copper-trafficking role and may include storage of labile copper, modulation of transcription, and antioxidant defense. The conserved metal binding site of Atox1, CxGC, differs from the metal-binding sites of copper-transporting ATPases and has a physiologically relevant redox potential that equilibrates with the GSH:GSSG pair. Critical Issues: Tight relationship appears to exist between intracellular copper levels and glutathione (GSH) homeostasis. The biochemical properties of Atox1 place it at the intersection of cellular networks that regulate copper distribution and cellular redox balance. Mechanisms through which Atox1 facilitates copper export and contributes to oxidative defense are not fully understood. Future Directions: The current picture of cellular redox homeostasis and copper physiology will be enhanced by further mechanistic studies of functional interactions between the GSH:GSSG pair and copper-trafficking machinery. Antioxid. Redox Signal. 19, 945–957. PMID:23249252

Metallic copper corrosion rates, moisture content, and growth medium influence survival of copper-ion resistant bacteria

PubMed Central

Elguindi, Jutta; Moffitt, Stuart; Hasman, Henrik; Andrade, Cassandra; Raghavan, Srini; Rensing, Christopher

2013-01-01

The rapid killing of various bacteria in contact with metallic copper is thought to be influenced by influx of copper ions into the cells but the exact mechanism is not fully understood. This study showed that the kinetics of contact-killing of copper surfaces depended greatly on the amount of moisture present, copper content of alloys, type of medium used, and type of bacteria. We examined antibiotic- and copper-ion resistant strains of Escherichia coli and Enterococcus faecium isolated from pig farms following the use of copper sulfate as feed supplement. The results showed rapid killing of both copper-ion resistant E. coli and E. faecium strains when samples in rich medium were spread in a thin, moist layer on copper alloys with 85% or greater copper content. E. coli strains were rapidly killed under dry conditions while E. faecium strains were less affected. Electroplated copper surface corrosion rates were determined from electro-chemical polarization tests using the Stern-Geary method and revealed decreased corrosion rates with benzotriazole and thermal oxide coating. Copper-ion resistant E. coli and E. faecium cells suspended in 0.8% NaCl showed prolonged survival rates on electroplated copper surfaces with benzotriazole coating and thermal oxide coating compared to surfaces without anti-corrosion treatment. Control of surface corrosion affected the level of copper ion influx into bacterial cells which contributed directly to bacterial killing. PMID:21085951

Release of Micronized Copper Particles from Pressure ...

EPA Pesticide Factsheets

Micronized copper pressure treated lumber (PTL) has recently been introduced to the consumer market as a replacement for ionized copper PTL. The presence of particulate rather than aqueous copper raises concerns about the exposure of humans as well as the environment to the particles. Two common pathways of exposure, leaching during contact with water and transfer during physical contact, were investigated to gage potential human and environmental risk during intended use of the product. Characterization, leaching tests, and wipe tests were conducted on two representative formulations of micronized copper PTL (micronized copper azole or MCA) to quantify the levels of copper present in the treated material and the amount of copper released during use as well as to determine the form (particle or ion) of the copper after it was released. Additionally, an ionized copper pressure treated wood (alkaline copper azole or ACA) was tested for comparison. The characterization showed that copper carbonate is the primary particle form in the MCA treated wood, but other forms are also present, particularly in the MCA-1 formulation, which contained a large amount of organically complexed copper. Microscopy showed that MCA-1 contained particles roughly half the size of MCA-2. The leaching results indicate that mostly (> ~95%) ionic copper is released from the MCA wood and that the particulate copper that was released is attached to cellulose and not free in solution. A sma

Intracellular Copper Does Not Catalyze the Formation of Oxidative DNA Damage in Escherichia coli▿

PubMed Central

Macomber, Lee; Rensing, Christopher; Imlay, James A.

2007-01-01

Because copper catalyzes the conversion of H2O2 to hydroxyl radicals in vitro, it has been proposed that oxidative DNA damage may be an important component of copper toxicity. Elimination of the copper export genes, copA, cueO, and cusCFBA, rendered Escherichia coli sensitive to growth inhibition by copper and provided forcing circumstances in which this hypothesis could be tested. When the cells were grown in medium supplemented with copper, the intracellular copper content increased 20-fold. However, the copper-loaded mutants were actually less sensitive to killing by H2O2 than cells grown without copper supplementation. The kinetics of cell death showed that excessive intracellular copper eliminated iron-mediated oxidative killing without contributing a copper-mediated component. Measurements of mutagenesis and quantitative PCR analysis confirmed that copper decreased the rate at which H2O2 damaged DNA. Electron paramagnetic resonance (EPR) spin trapping showed that the copper-dependent H2O2 resistance was not caused by inhibition of the Fenton reaction, for copper-supplemented cells exhibited substantial hydroxyl radical formation. However, copper EPR spectroscopy suggested that the majority of H2O2-oxidizable copper is located in the periplasm; therefore, most of the copper-mediated hydroxyl radical formation occurs in this compartment and away from the DNA. Indeed, while E. coli responds to H2O2 stress by inducing iron sequestration proteins, H2O2-stressed cells do not induce proteins that control copper levels. These observations do not explain how copper suppresses iron-mediated damage. However, it is clear that copper does not catalyze significant oxidative DNA damage in vivo; therefore, copper toxicity must occur by a different mechanism. PMID:17189367

Effect of dietary manganese on antioxidant status and expression levels of heat-shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

PubMed

Zhu, Yong-Wen; Lu, Lin; Li, Wen-Xiang; Zhang, Li-Yang; Ji, Cheng; Lin, Xi; Liu, Hsiao-Ching; Odle, Jack; Luo, Xu-Gang

2015-12-28

To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

The effects of CaEDTA injection on lead, zinc, copper and ALAD in erythrocyte, plasma and urine in lead-exposed workers: a 24-h observation.

PubMed

Aono, H; Araki, S

1984-01-01

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 micrograms/dl (mean 49 micrograms/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.

Copper Regulates Cyclic AMP-Dependent Lipolysis

PubMed Central

Krishnamoorthy, Lakshmi; Cotruvo, Joseph A.; Chan, Jefferson; Kaluarachchi, Harini; Muchenditsi, Abigael; Pendyala, Venkata S.; Jia, Shang; Aron, Allegra T.; Ackerman, Cheri M.; Vander Wal, Mark N.; Guan, Timothy; Smaga, Lukas P.; Farhi, Samouil L.; New, Elizabeth J.; Lutsenko, Svetlana; Chang, Christopher J.

2016-01-01

Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium, and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining the body's weight and energy stores. Utilizing a murine model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we demonstrate that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B. Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue within a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype. PMID:27272565

Use of Synchrotron X-ray Fluorescence to Measure Trace Metal Distribution in the Brain

NASA Astrophysics Data System (ADS)

Linkous, D.; Flinn, J. M.; Lanzirotti, A.; Frederickson, C.; Jones, B. F.; Bertsch, P. M.

2002-12-01

X26A, National Synchrotron Light Source, was used to quantitatively evaluate the spatial distribution of trace metals, such as Zn and Cu, in brain tissue. X-ray microprobe techniques offer distinct advantages over other analytical methods by allowing analyses to be done in-situ with little or no chemical pretreatment and low detection limits (about 1 ppm). In the context of neuroscience, SXRF can provide non-destructive measurements of specific metal concentrations and distribution within nerve (brain) tissue. Neuronal tissue from organisms having undergone different normal or experimental conditions may be compared, with analytical capacities not limited by binding states of the metal (i.e., vesicular or enzymatic), as is the case with staining techniques.. Whole regions of tissue may be scanned for detectable trace metals at spatial resolutions of 10um or less using focused monochromatic x-ray beams. Here special attention has been given to zinc because it is the most common trace metal in the brain, and levels have been increasing in the environment. In this investigation, zinc concentrations present within the hilus of a rat hippocampus, and to a lesser extent in the cortex, have been shown to increase following long-term ingestion of zinc-enhanced drinking water that was associated with deficits in spatial memory. Concomitantly, copper concentrations in the internal capsule were comparatively lower. Other first order transition metals, Cr, V, Mn, and Co were not detected. In contrast, elevated levels of Zn, Cu, and Fe have been seen in amyloid plaques associated with Alzheimer's disease.

Laboratory evolution of copper tolerant yeast strains

PubMed Central

2012-01-01

Background Yeast strains endowed with robustness towards copper and/or enriched in intracellular Cu might find application in biotechnology processes, among others in the production of functional foods. Moreover, they can contribute to the study of human diseases related to impairments of copper metabolism. In this study, we investigated the molecular and physiological factors that confer copper tolerance to strains of baker's yeasts. Results We characterized the effects elicited in natural strains of Candida humilis and Saccharomyces cerevisiae by the exposure to copper in the culture broth. We observed that, whereas the growth of Saccharomyces cells was inhibited already at low Cu concentration, C. humilis was naturally robust and tolerated up to 1 g · L-1 CuSO4 in the medium. This resistant strain accumulated over 7 mg of Cu per gram of biomass and escaped severe oxidative stress thanks to high constitutive levels of superoxide dismutase and catalase. Both yeasts were then "evolved" to obtain hyper-resistant cells able to proliferate in high copper medium. While in S. cerevisiae the evolution of robustness towards Cu was paralleled by the increase of antioxidative enzymes, these same activities decreased in evolved hyper-resistant Candida cells. We also characterized in some detail changes in the profile of copper binding proteins, that appeared to be modified by evolution but, again, in a different way in the two yeasts. Conclusions Following evolution, both Candida and Saccharomyces cells were able to proliferate up to 2.5 g · L-1 CuSO4 and to accumulate high amounts of intracellular copper. The comparison of yeasts differing in their robustness, allowed highlighting physiological and molecular determinants of natural and acquired copper tolerance. We observed that different mechanisms contribute to confer metal tolerance: the control of copper uptake, changes in the levels of enzymes involved in oxidative stress response and changes in the copper-binding proteome. However, copper elicits different physiological and molecular reactions in yeasts with different backgrounds. PMID:22214286

Copper, iron, and selenium dietary deficiencies negatively impact skeletal integrity: A review.

PubMed

Medeiros, Denis M

2016-06-01

Nutrients have been known to have a significant role in maintaining the health of the skeleton, both bone and cartilage. The nutrients that have received the majority of the attention are Vitamin D and calcium. However, limited attention has been directed toward three trace elements that may have mechanistic impact upon the skeletal tissues and could compromise skeletal health resulting from inadequate intakes of copper, iron, and selenium. The role of copper and selenium has been known, but the role of iron has only received recent attention. Copper deficiency is thought to impact bone health by a decrease in lysyl oxidase, a copper-containing enzyme, which facilitates collagen fibril crosslinking. Iron deficiency impact upon bone has only recently been discovered but the exact mechanism on how the deficient states enhance bone pathology is speculative. Selenium deficiency has an impact on cartilage thereby having an indirect impact on bone. However, several studies suggest that a mycotoxin when consumed by humans is the culprit in some cartilage disorders and the presence of selenium could attenuate the pathology. This review summarizes the current knowledge base with respect to skeletal integrity when each of these three trace elements are inadequate in diets of both animals and humans. © 2016 by the Society for Experimental Biology and Medicine.

Reliable porcine coronary model of chronic total occlusion using copper wire stents and bioabsorbable levo-polylactic acid polymer.

PubMed

Sim, Doo Sun; Jeong, Myung Ho; Cha, Kyoung Rae; Park, Suk Ho; Park, Jong Oh; Shin, Young Min; Shin, Heungsoo; Hong, Young Joon; Ahn, Youngkeun; Schwartz, Robert S; Kang, Jung Chaee

2012-12-01

Chronic total occlusion (CTO) remains a challenge in interventional cardiology. We investigated the feasibility and reliability of copper wire stents and levo-polylactic acid (l-PLA) as a means of CTO induction in a porcine model. In one group of 20 swine, copper stents were crimped on a 3.0mm angioplasty balloon and inserted into the mid-left anterior descending coronary artery (LAD). In the other group of 20 swine, l-PLA was wrapped on a guidewire and pushed into the distal LAD with a 3.0mm balloon catheter to induce embolization. Of 20 swine which underwent copper stent implantation, 13 died of stent thrombosis. In the remaining 7 swine, total or near total occlusion with collateral circulation was observed at 5 weeks. Of 20 swine which underwent l-PLA embolization, 4 died of ventricular fibrillation during or shortly after the procedure. Serial histopathologic studies showed complete absorption of the polymer with replacement by fibrotic tissue approximately 4 weeks following the polymer implantation. CTO could be reliably induced in porcine coronary arteries by copper stents and l-PLA. These models may support investigation of new percutaneous devices to facilitate CTO interventions. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Toxicity and deficiency of copper in Elsholtzia splendens affect photosynthesis biophysics, pigments and metal accumulation.

PubMed

Peng, Hongyun; Kroneck, Peter M H; Küpper, Hendrik

2013-06-18

Elsholtzia splendens is a copper-tolerant plant species growing on copper deposits in China. Spatially and spectrally resolved kinetics of in vivo absorbance and chlorophyll fluorescence in mesophyll of E. splendens were used to investigate the copper-induced stress from deficiency and toxicity as well as the acclimation to excess copper stress. The plants were cultivated in nutrient solutions containing either Fe(III)-EDTA or Fe(III)-EDDHA. Copper toxicity affected light-acclimated electron flow much stronger than nonphotochemical quenching (NPQ) or dark-acclimated photochemical efficiency of PSIIRC (Fv/Fm). It also changed spectrally resolved Chl fluorescence kinetics, in particular by strengthening the short-wavelength (<700 nm) part of NPQ altering light harvesting complex II (LHCII) aggregation. Copper toxicity reduced iron accumulation, decreased Chls and carotenoids in leaves. During acclimation to copper toxicity, leaf copper decreased but leaf iron increased, with photosynthetic activity and pigments recovering to normal levels. Copper tolerance in E. splendens was inducible; acclimation seems be related to homeostasis of copper and iron in E. splendens. Copper deficiency appeared at 10 mg copper per kg leaf DW, leading to reduced growth and decreased photosynthetic parameters (F0, Fv/Fm, ΦPSII). The importance of these results for evaluating responses of phytoremediation plants to stress in their environment is discussed.

Incorporation of copper nanoparticles into paper for point-of-use water purification

PubMed Central

Smith, James A.

2014-01-01

As a cost-effective alternative to silver nanoparticles, we have investigated the use of copper nanoparticles in paper filters for point-of-use water purification. This work reports an environmentally benign method for the direct in situ preparation of copper nanoparticles (CuNPs) in paper by reducing sorbed copper ions with ascorbic acid. Copper nanoparticles were quickly formed in less than 10 minutes and were well distributed on the paper fiber surfaces. Paper sheets were characterized by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, and atomic absorption spectroscopy. Antibacterial activity of the CuNP sheets was assessed for by passing Escherichia coli bacteria suspensions through the papers. The effluent was analyzed for viable bacteria and copper release. The CuNP papers with higher copper content showed a high bacteria reduction of log 8.8 for E. coli. The paper sheets containing copper nanoparticles were effective in inactivating the test bacteria as they passed through the paper. The copper levels released in the effluent water were below the recommended limit for copper in drinking water (1 ppm). PMID:25014431

Selected organic compounds and trace elements in streambed sediments and fish tissues, Cook Inlet Basin, Alaska

USGS Publications Warehouse

Frenzel, Steven A.

2000-01-01

Organochlorines, semivolatile organic compounds (SVOCs), and trace elements were investigated in streambed sediments and fish tissues at selected sites in the Cook Inlet Basin, Alaska, during 1998. At most sites, SVOCs and organochlorine compounds were either not detected or detected at very low concentrations. Chester Creek at Arctic Boulevard at Anchorage, which was the only site sampled with a significant degree of development in the watershed, had elevated levels of many SVOCs in streambed sediment. Coring of sediments from two ponds on Chester Creek confirmed the presence of elevated concentrations of a variety of organic compounds. Moose Creek, a stream with extensive coal deposits in its watershed, had low concentrations of numerous SVOCs in streambed sediment. Three sites located in national parks or in a national wildlife refuge had no detectable concentrations of SVOCs. Trace elements were analyzed in both streambed sediments and tissues of slimy sculpin. The two media provided similar evidence for elevated concentrations of cadmium, lead, and zinc at Chester Creek. In this study, 'probable effect levels '(PELs) were determined from sediments finer than 0.063 millimeters, where concentrations tend to be greatest. Arsenic and chromium concentrations exceeded the PEL at eight and six sites respectively. Zinc exceeded the PEL at one site. Cadmium and copper concentrations were smaller than the PEL at all sites. Mercury concentrations in streambed sediments from the Deshka River were near the PEL, and selenium concentrations at that site also appear to be elevated above background levels. At half the sites where slimy sculpin were sampled, selenium concentrations were at levels that may cause adverse effects in some species.

Ethanol exposure induces oxidative stress and impairs nitric oxide availability in the human placental villi: a possible mechanism of toxicity.

PubMed

Kay, H H; Grindle, K M; Magness, R R

2000-03-01

We undertook this investigation to explore the effects of ethanol exposure on nitric oxide synthase levels and nitric oxide release. Our hypothesis was that ethanol exposure modifies nitric oxide activity within the placenta as a result of oxidative stress. Four 10-g samples of term normal human placental villous tissue were perifused with nonrecirculating Dulbecco's modified Eagle's medium and 25-mmol/L N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] with 0-, 50-, 100-, or 200-mmol/L ethanol. After 2 hours of exposure, tissue was removed, fixed, and frozen for analysis. Immunohistochemical analysis was performed for subtype I or neuronal nitric oxide synthase (nNOS), subtype II or inducible nitric oxide synthase (iNOS), and subtype III or endothelial nitric oxide synthase (eNOS) localization. Western blot analysis was performed for eNOS quantitation. Cyclic guanosine monophosphate and copper-zinc superoxide dismutase levels were measured by electroimmunoassay and kinetic assay, respectively. Nitric oxide release was analyzed by a Sievers nitric oxide analyzer. Immunohistochemical examination confirmed that only eNOS was localized to the syncytiotrophoblasts. After ethanol exposure, eNOS protein expression increased 2.5- to 3.0-fold over that of the control. Tissue cyclic guanosine monophosphate content and nitric oxide release into the effluent were decreased, whereas superoxide dismutase levels were increased at higher ethanol levels (P <.05). Ethanol exposure appears to induce oxidative stress, which may account for the decreased nitric oxide release, because nitric oxide may be shunted toward scavenging free radicals. Increased eNOS protein expression may be a response to the increased demand for nitric oxide. Decreased nitric oxide availability could adversely affect placental blood flow regulation, which could, in turn, account for the growth restriction seen in ethanol-exposed fetuses.

Potential role of peroxisome proliferator activated receptor gamma activation on serum visfatin and trace elements in high fat diet induced type 2 diabetes mellitus.

PubMed

Tabassum, Arshia; Zaidi, Syeda Nuzhat Fatima; Yasmeen, Kausar; Mahboob, Tabassum

2018-07-15

Electrolytes and trace elements dysregulation play an important role in the progression of obesity and diabetes complications. The present study was designed to evaluate the insulin sensitizing effects of peroxisomes proliferators activated receptor gamma (PPAR-γ) agonist on trace elements in obesity induced type 2 diabetes mellitus and correlate with serum visfatin. Wistar rats were categorized into five groups. Group I served as control; Group II fed on high fat diet (HFD); Group III fed on HFD and treated with rosiglitazone (3 mg/kg) for 7 days; Group IV were T2DM rats induce by HFD and low dose of streptozotocin (i.p. 35 mg/kg); Group V was T2DM rats treated with rosiglitazone (3 mg/kg) for 7 days. Serum and tissues electrolytes levels and renal, hepatic and cardiac tissues trace elements were estimated by flame photometer and atomic absorption spectroscopy. Serum visfatin was estimated by ELISA. Pearson correlations were analyzed among fasting blood glucose (FBG), serum visfatin and tissues trace elements. Results of the current study showed hyponatremia, hyperkalemia, hypomagnesemia and hypercalcemia in HFD and T2DM groups. HFD and T2DM also showed elevated copper and iron levels; however, zinc and selenium levels were decreased. Rosiglitazone treatment increased the insulin sensitization and altered these changes. A Strong association was observed among FBG, serum visfatin and trace elements levels of HFD and T2DM. Obesity and diabetes mellitus disturbed visfatin, electrolytes and trace elements homeostasis. Rosiglitazone treatment restored these changes. The results of the study could serve as a basis for further studies for the prevention of diabetic complications. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular control of copper homeostasis in filamentous fungi: increased expression of a metallothionein gene during aging of Podospora anserina.

PubMed

Averbeck, N B; Borghouts, C; Hamann, A; Specke, V; Osiewacz, H D

2001-01-01

The lifespan of the ascomycete Podospora anserina was previously demonstrated to be significantly increased in a copper-uptake mutant, suggesting that copper is a potential stressor involved in degenerative processes. In order to determine whether changes in copper stress occur in the cells during normal aging of cultures, we cloned and characterized a gene coding for a component of the molecular machinery involved in the control of copper homeostasis. This gene, PaMt1, is a single-copy gene that encodes a metallothionein of 26 amino acids. The coding sequence of PaMt1 is interrupted by a single intron. The deduced amino acid sequence shows a high degree of sequence identity to metallothioneins of the filamentous ascomycete Neurospora crassa and the basidiomycete Agaricus bisporus, and to the N-terminal portion of mammalian metallothioneins. Levels of PaMt1 transcript increase in response to elevated amounts of copper in the growth medium and during aging of wild-type cultures. In contrast, in the long-lived mutant grisea, transcript levels first increase but then decrease again. The ability of wild-type cultures to respond to exogenous copper stress via the induction of PaMt1 transcription is not affected as they grow older.

NOTE: A positive contrast, tri-modality tissue marker for breast tumour localization

NASA Astrophysics Data System (ADS)

Li, Yangmei; Xiong Wang, Jian; Holloway, Claire; Plewes, Donald B.

2007-02-01

A new interstitial breast localization marker is proposed which exhibits positive contrast in T1-weighted MRI, ultrasound and x-ray mammography. Unlike previous markers which provide MRI contrast on the basis of a susceptibility-induced signal void, this marker provides a clear positive contrast without any loss of signal or spatial distortion. The marker is composed of 400 µm diameter copper microspheres suspended in a Gd-DTPA-doped gel matrix. Optimal contrast in T1-weighted spoiled gradient recalled MRI was found to occur with the addition of 10 mM Gd-DTPA. Ultrasound contrast was generated on the basis of scattering from the copper microspheres. X-ray contrast was provided by the high x-ray attenuation properties of the copper microspheres. The study demonstrates potential suitability of the marker for use as a breast localization marker based on ex vivo studies of chicken breast.

Distribution of heavy metals in internal organs and tissues of Korean molluscan shellfish and potential risk to human health.

PubMed

Mok, Jong Soo; Kwon, Ji Young; Son, Kwang Tae; Choi, Woo Seok; Kim, Poong Ho; Lee, Tae Seek; Kim, Ji Hoe

2015-09-01

Molluscan shellfish (gastropods and bivalves) were collected from major fish markets on the Korean coast and analyzed for mercury by direct Hg analyzer and for other metals, such as cadmium, lead, chromium, silver, nickel, copper and zinc, using inductively coupled plasma mass spectrometry. Distribution of heavy metals in muscles, internal organs and whole tissues were determined and a potential risk assessment was conducted to evaluate their hazard for human consumption. Heavy metals were accumulated significantly higher (P < 0.05) in internal organs than in muscles for all species. The mean Cd level, which had the highest level of three hazardous metals (Cd, Pb, and Hg) in all internal-organ samples were above the regulatory limit of Korea and the mean level in whole tissue samples of the selected gastropod species, bay scallop and comb pen shell, exceeded the limit (except in a few cases). The sum of the estimated dietary intake of Cd, Pb and Hg for each part of all tested species accounted for 1.59-16.94, 0.02-0.36, and 0.07-0.16% respectively, of the provisional tolerable daily intake adopted by the Joint FAO/WHO Expert Committee on Food Additives. The hazard index for each part of gastropods and bivalves was below 1.0, however, the maximum HI for internal organs of all analysed species was quite high (0.71). These results suggest that consumption of flesh after removing the internal organs of some molluscan shellfish (all gastropod species, bay scallop and comb pen shell) is a suitable way for reducing Cd exposure.

Efficacy of copper borax preservative against wood decay

Treesearch

William Abbott; Bessie Woodward; Michael West

2001-01-01

In this study, a wood preservative containing active ingredients of 43.5% borax and 3.1% copper hydroxide was evaluated in soil-block tests in accordance with AWPA E10. Results suggested thatthe copper hydroxide was not contributing to fungal toxicity at preservative threshold levels. Thresholds determined for this preservative were very close to those previously...

High serum copper level is associated with an increased risk of preeclampsia in Asians: A meta-analysis.

PubMed

Song, Xingxing; Li, Bingrong; Li, Zongyao; Wang, Jiantao; Zhang, Dongfeng

2017-03-01

Epidemiological studies evaluating the associations between serum copper and ratios of Cu/Zn and the preeclampsia (PE) risk in Asian population have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize the relationships. We hypothesize that higher serum copper and ratios of Cu/Zn may increase the PE risk. A systematic literature search was performed in PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), VIP (Database of Chinese Scientific and Technical Periodicals) and Wangfang databases for relevant studies up to November 2016. Pooled standardized mean difference (SMD) was calculated with random effects model. The results showed that PE patients had a higher serum copper level [SMD (95% CI): 1.05 (0.34, 1.77), Z=2.88, P for Z=0.004; I 2 =96.9%, P for I 2 <0.0001] compared with healthy pregnancy controls. In subgroup analyses, a higher serum copper level in PE patients was observed in case-control studies [SMD (95% CI): 1.39 (0.44, 2.34)]. No significant difference was found between PE patients and healthy pregnancy controls for ratios of Cu/Zn [(SMD (95% CI): 0.26 (-0.77, 1.29), Z=0.49, P for Z=0.625; I 2 =95.8%, P for I 2 <0.0001)]. In conclusion, our meta-analysis indicates that a higher serum copper level is associated with an increased risk of PE. Further studies are needed to confirm these results in future research. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of copper supplement on growth and viability of strains used as starters and adjunct cultures for Emmental cheese manufacture.

PubMed

Rodríguez, L Mato; Alatossava, T

2008-10-01

To determine the effects of supplemented copper (Cu2+) on growth and viability of strains used as starters and adjunct cultures for Emmental cheese manufacture. Thirteen strains belonging to Lactobacillus delbrueckii, Lactobacillus helveticus, Lactobacillus rhamnosus, Streptococcus thermophilus or Propionibacterium freudenreichii species were exposed to various copper concentrations in the proper growth medium at relevant growth temperatures, and the effects of supplemented copper on bacterial growth and cell viability were determined by optical density and pH measurements, also by platings. Among the species considered, L. delbrueckii was the most copper resistant and S. thermophilus the most sensitive to copper. Anaerobic conditions increased this sensitivity significantly. There was also a considerable amount of variation in copper resistance at strain level. Copper resistance is both a species- and strain-dependent property and may reflect variability in copper-binding capacities by cell wall components among species and strains. In addition, the chemical state of copper may be involved. This study revealed that copper resistance is a highly variable property among starter and adjunct strains, and this variability should be considered when strains are selected for Emmental cheese manufacture.

Textured carbon on copper: A novel surface with extremely low secondary electron emission characteristics

NASA Technical Reports Server (NTRS)

Curren, A. N.; Jensen, K. A.

1985-01-01

Experimentally determined values of true secondary electron emission and relative values of reflected primary electron yield for a range of primary electron beam energies and beam impingement angles are presented for a series of novel textured carbon surfaces on copper substrates. (All copper surfaces used in this study were oxygen-free, high-conductivity grade). The purpose of this investigation is to provide information necessary to develop high-efficiency multistage depressed collectors (MDC's) for microwave amplifier traveling-wave tubes (TWT's) for communications and aircraft applications. To attain the highest TWT signal quality and overall efficiency, the MDC electrode surface must have low secondary electron emission characteristics. While copper is the material most commonly used for MDC electrodes, it exhibits relatively high levels of secondary electron emission unless its surface is treated for emission control. The textured carbon surface on copper substrate described in this report is a particularly promising candidate for the MDC electrode application. Samples of textured carbon surfaces on copper substrates typical of three different levels of treatment are prepared and tested for this study. The materials are tested at primary electron beam energies of 200 to 2000 eV and at direct (0 deg) to near-grazing (85 deg) beam impingement angles. True secondary electron emission and relative reflected primary electron yield characteristics of the textured surfaces are compared with each other and with those of untreated copper. All the textured carbon surfaces on copper substrate tested exhibited sharply lower secondary electron emission characteristics than those of an untreated copper surface.

Cadmium, copper, lead and zinc contents of the mangrove oyster, Crassostrea corteziensis, of seven coastal lagoons of NW Mexico.

PubMed

Frías-Espericueta, M G; Osuna-López, I; Bañuelos-Vargas, I; López-López, G; Muy-Rangel, M D; Izaguirre-Fierro, G; Rubio-Carrasco, W; Meza-Guerrero, P C; Voltolina, D

2009-10-01

The ranges of concentrations of Cd, Cu, Pb and Zn of the soft tissues of C. corteziensis collected in seven coastal lagoons of NW Mexico were 1.55-7.45, 17.50-166.36, 4.13-9.49 and 245.34-2,304.12 microg/g (dry weight), respectively. Their distributions were not consistent and there were no seasonal trends, indicating different point sources of the metals in each lagoon. The mean Cd and Pb concentrations were 5.34 and 6.30 microg/g (dry weight), which are higher than the values indicative of polluted areas. Our data indicate that only the levels of Cd are a possible health risk in six of these lagoons, and only in the case of regular local consumers. In one, Cu and Zn reach levels of concern.

Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, R.R.; Naftel, S.J.; Nelson, A.J.

2010-03-16

Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, coppermore » and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.« less

Serum zinc, copper and iron status of children with coeliac disease on three months of gluten-free diet with or without four weeks of zinc supplements: a randomised controlled trial.

PubMed

Negi, K; Kumar, R; Sharma, L; Datta, S P; Choudhury, M; Kumar, P

2018-04-01

Data about the effect of zinc supplementation with gluten-free diet on normalisation of plasma zinc, copper and iron in patients with coeliac disease are scanty. We evaluated the effect of zinc supplementation on serum zinc, copper and iron levels in patients with coeliac disease, by randomising 71 children newly diagnosed with coeliac disease into two groups: Group A = gluten-free diet (GFD); and Group B = gluten-free diet with zinc supplements (GFD +Zn). The rise in iron and zinc was significantly higher in the latter, but the mean rise of copper levels was slightly higher in the former, but the difference was not significant.

The effects of low-level ionizing radiation and copper exposure on the incidence of antibiotic resistance in lentic biofilm bacteria.

PubMed

McArthur, J Vaun; Dicks, Christian A; Bryan, A Lawrence; Tuckfield, R Cary

2017-09-01

Environmental reservoirs of antibiotic resistant bacteria are poorly understood. Understanding how the environment selects for resistance traits in the absence of antibiotics is critical in developing strategies to mitigate this growing menace. Indirect or co-selection of resistance by environmental pollution has been shown to increase antibiotic resistance. However no attention has been given to the effects of low-level ionizing radiation or the interactions between radiation and heavy metals on the maintenance or selection for antibiotic resistance (AR) traits. Here we explore the effect of radiation and copper on antibiotic resistance. Bacteria were collected from biofilms in two ponds - one impacted by low-level radiocesium and the other an abandoned farm pond. Through laboratory controlled experiments we examined the effects of increasing concentrations of copper on the incidence of antibiotic resistance. Differences were detected in the resistance profiles of the controls from each pond. Low levels (0.01 mM) of copper sulfate increased resistance but 0.5 mM concentrations of copper sulfate depressed the AR response in both ponds. A similar pattern was observed for levels of multiple antibiotic resistance per isolate. The first principal component response of isolate exposure to multiple antibiotics showed significant differences among the six isolate treatment combinations. These differences were clearly visualized through a discriminant function analysis, which showed distinct antibiotic resistance response patterns based on the six treatment groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systems Biology Approach in Chlamydomonas Reveals Connections between Copper Nutrition and Multiple Metabolic Steps[C][W][OA

PubMed Central

Castruita, Madeli; Casero, David; Karpowicz, Steven J.; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I.; Yan, Weihong; Cokus, Shawn; Loo, Joseph A.; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S.

2011-01-01

In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper. PMID:21498682

Juvenile roach (Rutilus rutilus) increase their anaerobic metabolism in response to copper exposure in laboratory conditions.

PubMed

Maes, Virginie; Betoulle, Stéphane; Jaffal, Ali; Dedourge-Geffard, Odile; Delahaut, Laurence; Geffard, Alain; Palluel, Olivier; Sanchez, Wilfried; Paris-Palacios, Séverine; Vettier, Aurélie; David, Elise

2016-07-01

This study aims to determine the potential impairment of cell energy synthesis processes (glycolysis and respiratory chain pathways) by copper in juvenile roach at different regulation levels by using a multi-marker approach. Juvenile roach were exposed to 0, 10, 50, and 100 µg/L of copper for 7 days in laboratory conditions. The glycolysis pathway was assessed by measuring the relative expression levels of 4 genes encoding glycolysis enzymes. The respiratory chain was studied by assessing the electron transport system and cytochrome c oxidase gene expression. Muscle mitochondria ultrastructure was studied, and antioxidant responses were measured. Furthermore, the main energy reserves-carbohydrates, lipids, and proteins-were measured, and cellular energy was evaluated by measuring ATP, ADP, AMP and IMP concentrations. This study revealed a disturbance of the cell energy metabolism due to copper exposure, with a significant decrease in adenylate energy charge in roach exposed to 10 μg/L of copper after 1 day. Moreover, ATP concentrations significantly decreased in roach exposed to 10 μg/L of copper after 1 day. This significant decrease persisted in roach exposed to 50 µg/L of copper after 7 days. AMP concentrations increased in all contaminated fish after 1 day of exposure. In parallel, the relative expression of 3 genes encoding for glycolysis enzymes increased in all contaminated fish after 1 day of copper exposure. Focusing on the respiratory chain, cytochrome c oxidase gene expression also increased in all contaminated fish at the two time-points. The activity of the electron transport system was not disturbed by copper, except in roach exposed to 100 µg/L of copper after 1 day. Copper induced a metabolic stress. Juvenile roach seemed to respond to the ensuing high energy demand by increasing their anaerobic metabolism, but the energy produced by the anaerobic metabolism is unable to compensate for the stress induced by copper after 7 days. This multi-marker approach allows us to reach a greater understanding of the effects of copper on the physiological responses of juvenile roach.

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre.

PubMed

Gheorghe, Liana; Popescu, Irinel; Iacob, Speranta; Gheorghe, Cristian; Vaidan, Roxana; Constantinescu, Alexandra; Iacob, Razvan; Becheanu, Gabriel; Angelescu, Corina; Diculescu, Mircea

2004-09-01

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10. There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

Effects of Copper Addition on Copper Resistance, Antibiotic Resistance Genes, and intl1 during Swine Manure Composting

PubMed Central

Yin, Yanan; Gu, Jie; Wang, Xiaojuan; Song, Wen; Zhang, Kaiyu; Sun, Wei; Zhang, Xin; Zhang, Yajun; Li, Haichao

2017-01-01

Copper is one of the most abundant heavy metals present in swine manure. In this study, a laboratory-scale aerobic composting system was amended with Cu at three levels (0, 200, and 2000 mg kg-1, i.e., control, Cu200, and Cu2000 treatments, respectively) to determine its effect on the fate of copper resistance genes [copper resistance genes (CRGs): pcoA, cusA, copA, and tcrB], antibiotic resistance genes [antibiotic resistance genes (ARGs): erm(A) and erm(B)], and intl1. The results showed that the absolute abundances of pcoA, tcrB, erm(A), erm(B), and intl1 were reduced, whereas those of copA and cusA increased after swine manure composting. Redundancy analysis showed that temperature significantly affected the variations in CRGs, ARGs, and intl1. The decreases in CRGs, ARGs, and intI1 were positively correlated with the exchangeable Cu levels. The bacterial community could be grouped according to the composting time under different treatments, where the high concentration of copper had a more persistent effect on the bacterial community. Network analysis determined that the co-occurrence of CRGs, ARGs, and intI1, and the bacterial community were the main contributors to the changes in CRGs, ARG, and intl1. Thus, temperature, copper, and changes in the bacterial community composition had important effects on the variations in CRGs, ARGs, and intl1 during manure composting in the presence of added copper. PMID:28316595

Copper speciation in the gill microenvironment of carp (Cyprinus carpio) at various levels of pH.

PubMed

Tao, Shu; Long, Aimin; Xu, Fuliu; Dawson, R W

2002-07-01

The fish gill microenvironment of Cyprinus carpio under stress of copper exposure was investigated. pH and other parameters including free copper activity, alkalinity, and inorganic and organic carbons in the surrounding water (inspired water) and in the gill microenvironment (expired water) were measured or calculated at various levels of pH and varying total copper concentrations. The chemical equilibrium calculation (from MINEQA2) and complexation modeling (mucus-copper) were coupled to calculate both species distribution. The results indicate that the pH in the fish gill microenvironment was different from that in the surrounding water with a balance point around 6.9. The secretion of both CO(2) and mucus was affected in both linear and nonlinear ways when the fish were exposed to elevated concentrations of copper. The complexation capacity of the gill mucus was characterized by a conditional stability constant (logk(Cu-mucus)) of 5.37 along with a complexation equivalent concentration (L(Cu-mucus)) of 0.96 mmol Cu/mg C. For both the fish microenvironment and the surrounding water, the dominant copper species shifted from Cu(2+) to CuCO(3)(0) and to Cu(OH)(2)(0) when the pH of the surrounding water changed from 6.12 to 8.11. The change in copper speciation in the gill microenvironment is smaller than that in the surrounding water due to the pH buffering capacity of the fish gills.

Socio-demographic, lifestyle, and dietary determinants of essential and possibly-essential trace element levels in adipose tissue from an adult cohort.

PubMed

Rodríguez-Pérez, Celia; Vrhovnik, Petra; González-Alzaga, Beatriz; Fernández, Mariana F; Martin-Olmedo, Piedad; Olea, Nicolás; Fiket, Željka; Kniewald, Goran; Arrebola, Juan P

2018-05-01

There is increasing evidence linking levels of trace elements (TEs) in adipose tissue with certain chronic conditions (e.g., diabetes or obesity). The objectives of this study were to assess concentrations of a selection of nine essential and possibly-essential TEs in adipose tissue samples from an adult cohort and to explore their socio-demographic, dietary, and lifestyle determinants. Adipose tissue samples were intraoperatively collected from 226 volunteers recruited in two public hospitals from Granada province. Trace elements (Co, Cr, Cu, Fe, Mn, Mo, Se, V, and Zn) were analyzed in adipose tissue by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Data were collected on socio-demographic characteristics, lifestyle, diet, and health status by face-to-face interview. Predictors of TE concentrations were assessed by using multivariable linear and logistic regression. All TEs were detected in all samples with the exception of Se (53.50%). Iron, zinc, and copper showed the highest concentrations (42.60 mg/kg, 9.80 mg/kg, and 0.68 mg/kg, respectively). Diet was the main predictor of Cr, Fe, Mo, and Se concentrations. Body mass index was negatively associated with all TEs (β coefficients = -0.018 to -0.593, p = 0.001-0.090) except for Mn and V. Age showed a borderline-significant positive correlation with Cu (β = 0.004, p = 0.089). Residence in a rural or semi-rural area was associated with increased Co, Cr, Fe, Mo, Mn, V and Zn concentrations and with β coefficients ranging from 0.196 to 0.544 (p < 0.05). Furthermore, individuals with higher educational level showed increased Cr, Co, Fe and V concentrations (β coefficients = 0.276-0.368, p = 0.022-0.071). This is the first report on the distribution of these TEs in adipose tissue and on their determinants in a human cohort and might serve as an initial step in the elucidation of their clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Examining mechanism of toxicity of copper oxide nanoparticles to Saccharomyces cerevisiae and Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Mashock, Michael J.

Copper oxide nanoparticles (CuO NPs) are an up and coming technology increasingly being used in industrial and consumer applications and thus may pose risk to humans and the environment. In the present study, the toxic effects of CuO NPs were studied with two model organisms Saccharomyces cerevisiae and Caenorhabditis elegans. The role of released Cu ions during dissolution of CuO NPs in growth media were studied with freshly suspended, aged NPs, and the released Cu 2+ fraction. Exposures to the different Cu treatments showed significant inhibition of S. cerevisiae cellular metabolic activity. Inhibition from the NPs was inversely proportional to size and was not fully explained by the released Cu ions. S. cerevisiae cultures grown under respiring conditions demonstrated greater metabolic sensitivity when exposed to CuO NPs compared to cultures undergoing fermentation. The cellular response to both CuO NPs and released Cu ions on gene expression was analyzed via microarray analysis after an acute exposure. It was observed that both copper exposures resulted in an increase in carbohydrate storage, a decrease in protein production, protein misfolding, increased membrane permeability, and cell cycle arrest. Cells exposed to NPs up-regulated genes related to oxidative phosphorylation but also may be inducing cell cycle arrest by a different mechanism than that observed with released Cu ions. The effect of CuO NPs on C. elegans was examined by using several toxicological endpoints. The CuO NPs displayed a more inhibitory effect, compared to copper sulfate, on nematode reproduction, feeding, and development. We investigated the effects of copper oxide nanoparticles and copper sulfate on neuronal health, a known tissue vulnerable to heavy metal toxicity. In transgenic C. eleganswith neurons expressing a green fluorescent protein reporter, neuronal degeneration was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, nematode mutant strains containing gene knockouts in the divalent-metal transporters smf-1 and smf-2 showed increased tolerance to copper exposure. These results lend credence to the hypothesis that some toxicological effects to eukaryotic organisms from copper oxide nanoparticle exposure may be due to properties specific to the nanoparticles and not solely from the released copper ions.

Isolating metal-tolerant bacteria capable of removing copper, chromium, and arsenic from treated wood

Treesearch

Carol A. Clausen

2000-01-01

Bioremediation of chromated copper arsenate-treated waste wood with one or more metal-tolerant bacteria is a potential method of naturally releasing metals from treated wood fibre. Sampling eight environments with elevated levels of copper, chromium, and arsenic resulted in the isolation of 28 bacteria with the capability of releasing one or more of the components from...

High copper level comulled and impregnated sulfur sorbent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, K.C.

A porous sulfur sorbent is disclosed which has principal use in desulfurizing reformer feedstreams. The sorbent is prepared by peptizing alumina with acid and mulling the peptized alumina with a copper compound to form an extrudable dough. The dough is extruded, dried and impregnated with additional copper. The resulting sorbent has a higher capacity for adsorbing sulfur compounds than conventional prior art materials.

Copper homeostasis gene discovery in Drosophila melanogaster.

PubMed

Norgate, Melanie; Southon, Adam; Zou, Sige; Zhan, Ming; Sun, Yu; Batterham, Phil; Camakaris, James

2007-06-01

Recent studies have shown a high level of conservation between Drosophila melanogaster and mammalian copper homeostasis mechanisms. These studies have also demonstrated the efficiency with which this species can be used to characterize novel genes, at both the cellular and whole organism level. As a versatile and inexpensive model organism, Drosophila is also particularly useful for gene discovery applications and thus has the potential to be extremely useful in identifying novel copper homeostasis genes and putative disease genes. In order to assess the suitability of Drosophila for this purpose, three screening approaches have been investigated. These include an analysis of the global transcriptional response to copper in both adult flies and an embryonic cell line using DNA microarray analysis. Two mutagenesis-based screens were also utilized. Several candidate copper homeostasis genes have been identified through this work. In addition, the results of each screen were carefully analyzed to identify any factors influencing efficiency and sensitivity. These are discussed here with the aim of maximizing the efficiency of future screens and the most suitable approaches are outlined. Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery.

Metal Dyshomeostasis and Inflammation in Alzheimer's and Parkinson's Diseases: Possible Impact of Environmental Exposures

PubMed Central

Myhre, Oddvar; Utkilen, Hans; Duale, Nur; Brunborg, Gunnar; Hofer, Tim

2013-01-01

A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is the only neuronal iron exporter, thereby subjecting it to lysosomal degradation. Subsequently raised neuronal iron levels can induce translation of the ferroportin assisting and copper binding amyloid precursor protein (APP); constitutive APP transmembrane passage lowers the copper pool which is important for many enzymes. Using in silico gene expression analyses, we here show significantly decreased expression of copper-dependent enzymes in AD brain and metallothioneins were upregulated in both diseases. Although few AD exposure risk factors are known, AD-related tauopathies can result from cyanobacterial microcystin and β-methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent risk factors for PD; for this disease neurodegeneration is likely to involve mitochondrial dysfunction, microglial activation, and neuroinflammation. Administration of metal chelators and anti-inflammatory agents could affect disease outcomes. PMID:23710288

Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials

NASA Astrophysics Data System (ADS)

Bastos, Carlos A. P.; Faria, Nuno; Ivask, Angela; Bondarenko, Olesja M.; Kahru, Anne; Powell, Jonathan

2018-04-01

Bacterial resistance to antimicrobial therapies is an increasing clinical problem. This is as true for topical applications as it is for systemic therapy. Topically, copper ions may be effective and cheap antimicrobials that act through multiple pathways thereby limiting opportunities to bacteria for resistance. However, the chemistry of copper does not lend itself to facile formulations that will readily release copper ions at biologically compatible pHs. Here, we have developed nanoparticulate copper hydroxide adipate tartrate (CHAT) as a cheap, safe, and readily synthesised material that should enable antimicrobial copper ion release in an infected wound environment. First, we synthesised CHAT and showed that this had disperse aquated particle sizes of 2-5 nm and a mean zeta potential of - 40 mV. Next, when diluted into bacterial medium, CHAT demonstrated similar efficacy to copper chloride against Escherichia coli and Staphylococcus aureus, with dose-dependent activity occurring mostly around 12.5-50 mg/L of copper. Indeed, at these levels, CHAT very rapidly dissolved and, as confirmed by a bacterial copper biosensor, showed identical intracellular loading to copper ions derived from copper chloride. However, when formulated at 250 mg/L in a topically applied matrix, namely hydroxyethyl cellulose, the benefit of CHAT over copper chloride was apparent. The former yielded rapid sustained release of copper within the bactericidal range, but the copper chloride, which formed insoluble precipitates at such concentration and pH, achieved a maximum release of 10 ± 7 mg/L copper by 24 h. We provide a practical formulation for topical copper-based antimicrobial therapy. Further studies, especially in vivo, are merited.

Boron-copper neutron absorbing material and method of preparation

DOEpatents

Wiencek, Thomas C.; Domagala, Robert F.; Thresh, Henry

1991-01-01

A composite, copper clad neutron absorbing material is comprised of copper powder and boron powder enriched with boron 10. The boron 10 content can reach over 30 percent by volume, permitting a very high level of neutron absorption. The copper clad product is also capable of being reduced to a thickness of 0.05 to 0.06 inches and curved to a radius of 2 to 3 inches, and can resist temperatures of 900.degree. C. A method of preparing the material includes the steps of compacting a boron-copper powder mixture and placing it in a copper cladding, restraining the clad assembly in a steel frame while it is hot rolled at 900.degree. C. with cross rolling, and removing the steel frame and further rolling the clad assembly at 650.degree. C. An additional sheet of copper can be soldered onto the clad assembly so that the finished sheet can be cold formed into curved shapes.

Circadian rhythm of blood and urinary copper in presumably healthy subjects of vegetarian food habit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, R.D.

Circadian rhythm of blood and urinary copper has been studied in presumably healthy subjects of a particular ethnic group in India who are vegetarians. A definite 24-hr variation has been observed for both blood and urinary copper. The peak for blood copper was 1500 hr and the lowest value was 0600 hr, with values of 0.185 mg/100 ml and 0.160 mg/100 ml respectively. The urinary peak and trough occurred at 0600 and 0300 hr, respectively. Remarkably higher 24-hr copper excretion values were noted (64.49 ..mu..g/day) with a range of 15-100 ..mu..g/day. The blood level of copper (0.134 mg/100 ml) remainedmore » within the range reported. One subject out of 25 deviated from the group with respect to circadian phasing and amplitude to urinary copper excretion. 20 references.« less

Stabilization of Oxidized Copper Nanoclusters in Confined Spaces

DOE PAGES

Akter, Nusnin; Wang, Mengen; Zhong, Jian-Qiang; ...

2018-01-04

Copper is an important industrial catalyst. The ability to manipulate the oxidation state of copper clusters in a controlled way is critical to understanding structure–reactivity relations of copper catalysts at the molecular level. Experimentally, cupric oxide surfaces or even small domains can only be stabilized at elevated temperatures and in the presence of oxygen, as copper can be easily reduced under reaction conditions. Herein bilayer silica films grown on a metallic substrate are used to trap diluted copper oxide clusters. By combining in situ experiments with first principles calculations, it is found that the confined space created by the silicamore » film leads to an increase in the energy barrier for Cu diffusion. Dispersed copper atoms trapped by the silica film can be easily oxidized by surface oxygen chemisorbed on the metallic substrate, which results in the formation and stabilization of Cu 2+ cations.« less

Cross-Comparison of Leaching Strains Isolated from Two Different Regions: Chambishi and Dexing Copper Mines

PubMed Central

Ngom, Baba; Liang, Yili; Liu, Xueduan

2014-01-01

A cross-comparison of six strains isolated from two different regions, Chambishi copper mine (Zambia, Africa) and Dexing copper mine (China, Asia), was conducted to study the leaching efficiency of low grade copper ores. The strains belong to the three major species often encountered in bioleaching of copper sulfide ores under mesophilic conditions: Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, and Leptospirillum ferriphilum. Prior to their study in bioleaching, the different strains were characterized and compared at physiological level. The results revealed that, except for copper tolerance, strains within species presented almost similar physiological traits with slight advantages of Chambishi strains. However, in terms of leaching efficiency, native strains always achieved higher cell density and greater iron and copper extraction rates than the foreign microorganisms. In addition, microbial community analysis revealed that the different mixed cultures shared almost the same profile, and At. ferrooxidans strains always outcompeted the other strains. PMID:25478575

Antibacterial, antibiofilm and antioxidant screening of copper(II)-complexes with some S-alkyl derivatives of thiosalicylic acid. Crystal structure of the binuclear copper(II)-complex with S-propyl derivative of thiosalicylic acid

NASA Astrophysics Data System (ADS)

Bukonjić, Andriana M.; Tomović, Dušan Lj.; Nikolić, Miloš V.; Mijajlović, Marina Ž.; Jevtić, Verica V.; Ratković, Zoran R.; Novaković, Slađana B.; Bogdanović, Goran A.; Radojević, Ivana D.; Maksimović, Jovana Z.; Vasić, Sava M.; Čomić, Ljiljana R.; Trifunović, Srećko R.; Radić, Gordana P.

2017-01-01

The spectroscopically predicted structure of the obtained copper(II)-complex with S-propyl derivative of thiosalicylic acid was confirmed by X-ray structural study. The binuclear copper(II)-complex with S-propyl derivative of thiosalicylic acid crystallized in two polymorphic forms with main structural difference in the orientation of phenyl rings relative to corresponding carboxylate groups. The antibacterial activity was tested determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by using microdilution method. The influence on bacterial biofilm formation was determined by tissue culture plate method. In general, the copper(II)-complexes manifested a selective and moderate activity. The most sensitive bacteria to the effects of Cu(II)-complexes was a clinical isolate of Pseudomonas aeruginosa. For this bacteria MIC and biofilm inhibitory concentration (BIC) values for all tested complexes were in the range or better than the positive control, doxycycline. Also, for the established biofilm of clinical isolate Staphylococcus aureus, BIC values for the copper(II)-complex with S-ethyl derivative of thiosalicylic acid,[Cu2(S-et-thiosal)4(H2O)2] (C3) and copper(II)-complex with S-butyl derivative of thiosalicylic acid, [Cu2(S-bu-thiosal)4(H2O)2] (C5) were in range or better than the positive control. All the complexes acted better against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus aureus ATCC 25923) than Gram-negative bacteria (Proteus mirabilis ATCC 12453, Pseudomonas aeruginosa, and P. aeruginosa ATCC 27855). The complexes showed weak antioxidative properties tested by two methods (1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assay).

Incorporation of copper nanoparticles into paper for point-of-use water purification.

PubMed

Dankovich, Theresa A; Smith, James A

2014-10-15

As a cost-effective alternative to silver nanoparticles, we have investigated the use of copper nanoparticles in paper filters for point-of-use water purification. This work reports an environmentally benign method for the direct in situ preparation of copper nanoparticles (CuNPs) in paper by reducing sorbed copper ions with ascorbic acid. Copper nanoparticles were quickly formed in less than 10 min and were well distributed on the paper fiber surfaces. Paper sheets were characterized by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, and atomic absorption spectroscopy. Antibacterial activity of the CuNP sheets was assessed for by passing Escherichia coli bacteria suspensions through the papers. The effluent was analyzed for viable bacteria and copper release. The CuNP papers with higher copper content showed a high bacteria reduction of log 8.8 for E. coli. The paper sheets containing copper nanoparticles were effective in inactivating the test bacteria as they passed through the paper. The copper levels released in the effluent water were below the recommended limit for copper in drinking water (1 ppm). Copyright © 2014 Elsevier Ltd. All rights reserved.

Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme*

PubMed Central

Bonnemaison, Mathilde L.; Bäck, Nils; Duffy, Megan E.; Ralle, Martina; Mains, Richard E.; Eipper, Betty A.

2015-01-01

The adaptor protein-1 complex (AP-1), which transports cargo between the trans-Golgi network and endosomes, plays a role in the trafficking of Atp7a, a copper-transporting P-type ATPase, and peptidylglycine α-amidating monooxygenase (PAM), a copper-dependent membrane enzyme. Lack of any of the four AP-1 subunits impairs function, and patients with MEDNIK syndrome, a rare genetic disorder caused by lack of expression of the σ1A subunit, exhibit clinical and biochemical signs of impaired copper homeostasis. To explore the role of AP-1 in copper homeostasis in neuroendocrine cells, we used corticotrope tumor cells in which AP-1 function was diminished by reducing expression of its μ1A subunit. Copper levels were unchanged when AP-1 function was impaired, but cellular levels of Atp7a declined slightly. The ability of PAM to function was assessed by monitoring 18-kDa fragment-NH2 production from proopiomelanocortin. Reduced AP-1 function made 18-kDa fragment amidation more sensitive to inhibition by bathocuproine disulfonate, a cell-impermeant Cu(I) chelator. The endocytic trafficking of PAM was altered, and PAM-1 accumulated on the cell surface when AP-1 levels were reduced. Reduced AP-1 function increased the Atp7a presence in early/recycling endosomes but did not alter the ability of copper to stimulate its appearance on the plasma membrane. Co-immunoprecipitation of a small fraction of PAM and Atp7a supports the suggestion that copper can be transferred directly from Atp7a to PAM, a process that can occur only when both proteins are present in the same subcellular compartment. Altered luminal cuproenzyme function may contribute to deficits observed when the AP-1 function is compromised. PMID:26170456

A novel nano-copper-bearing stainless steel with reduced Cu(2+) release only inducing transient foreign body reaction via affecting the activity of NF-κB and Caspase 3.

PubMed

Wang, Lei; Ren, Ling; Tang, Tingting; Dai, Kerong; Yang, Ke; Hao, Yongqiang

2015-01-01

Foreign body reaction induced by biomaterials is a serious problem in clinical applications. Although 317L-Cu stainless steel (317L-Cu SS) is a new type of implant material with antibacterial ability and osteogenic property, the foreign body reaction level still needs to be assessed due to its Cu(2+) releasing property. For this purpose, two macrophage cell lines were selected to detect cellular proliferation, apoptosis, mobility, and the secretions of inflammatory cytokines with the influence of 317L-Cu SS. Our results indicated that 317L-Cu SS had no obvious effect on the proliferation and apoptosis of macrophages; however, it significantly increased cellular migration and TNF-α secretion. Then, C57 mice were used to assess foreign body reaction induced by 317L-Cu SS. We observed significantly enhanced recruitment of inflammatory cells (primarily macrophages) with increased TNF-α secretion and apoptosis level in tissues around the materials in the early stage of implantation. With tissue healing, both inflammation and apoptosis significantly decreased. Further, we discovered that NF-κB pathway and Caspase 3 played important roles in 317L-Cu SS induced inflammation and apoptosis. We concluded that 317L-Cu SS could briefly promote the inflammation and apoptosis of surrounding tissues by regulating the activity of NF-κB pathway and Caspase 3. All these discoveries demonstrated that 317L-Cu SS has a great potential for clinical application.

Responses of hybrid striped bass to waterborne and dietary copper in freshwater and saltwater

USGS Publications Warehouse

Bielmyer, G.K.; Gatlin, D.; Isely, J.J.; Tomasso, J.; Klaine, S.J.

2005-01-01

Mechanisms of copper toxicity and consequences of exposure vary due to uptake route and ionoregulatory status. The goal of this research was to develop a model fish system to assess the influence of different Cu exposure routes (waterborne or dietary) on bioavailability, uptake, and effects in hybrid striped bass (Morone chrysops×Morone saxatilis) acclimated to fresh- or saltwater. Initially, hybrid striped bass were exposed to dietary Cu concentrations of 571, 785, and 1013 μg Cu/g, along with a control (∼ 5 μg Cu/g), for 14 days in saltwater. Intestinal and liver Cu accumulated in a dose-dependent manner in fish exposed to increasing levels of dietary Cu. Chronic (42 days) experiments were then conducted to determine sub-lethal effects of aqueous, dietary, and combined aqueous and dietary Cu exposures to both freshwater- and saltwater-acclimated hybrid striped bass. Growth and Cu accumulation in the gill, intestine, and liver were measured. Although no significant effects were observed in fish exposed to waterborne Cu, those exposed through the diet accumulated significant liver and intestinal Cu but showed no significant change in growth. Overall, these results suggest that at the levels tested, exposure to elevated waterborne Cu did not cause significant long-term tissue Cu accumulation, whereas dietary Cu exposure caused significant liver and intestinal Cu accumulation in hybrid striped bass which was comparable in both freshwater and saltwater (15 g/L).

Higher trophic level affects nutrient, silicon, metal(loid), and radionuclide mobilization from freshwater sediments

NASA Astrophysics Data System (ADS)

Schaller, Jörg; Planer-Friedrich, Britta

2017-04-01

Organic sediments in aquatic ecosystems are well known sinks for nutrients, silicon, and metal(loid)s. Organic matter-decomposing organisms like invertebrate shredders, grazers, bioturbators, and filter feeder are key-species for the carbon and energy turnover within the decomposer community. We could show that invertebrate shredders and grazer affect element fixation or remobilization by changing binding properties of organic sediments and the attached biofilm. Bioturbators affect element fixation or remobilization by changing redox conditions within the uppermost sediment layer. Last but not least filter feeders, like the zebra mussel Dreissena polymorpha, an invasive organism in North American and European freshwater ecosystems significantly contributed to element mobilization of silicon, iron, phosphorus, arsenic, and copper and to immobilization of uranium (p<0.001), probably driven by redox conditions, microbial activity within the gut system, or active control of element homeostasis. Except of the filter feeder D. polymorpha, the invertebrates are able to minimize the accumulation of non-nutrient elements due to specific strategies, which is an important strategy for species living in systems tending to element accumulation. However, D. polymorpha revealed a significant uptake and accumulation of arsenic, copper, iron, and especially uranium both into the soft body tissues and the seashell. This accumulation by D. polymorpha is in line with previous observations of metal(loid) accumulation from biomonitoring studies. In summary, higher trophic level strongly contributes to element fixation or remobilization in aquatic systems.

The effect of copper from water and food: changes of serum nonceruloplasmin copper and brain's amyloid-beta in mice.

PubMed

Wu, Min; Han, Feifei; Gong, Weisha; Feng, Lifang; Han, Jianzhong

2016-09-14

Copper is an essential element and also produces adverse health consequences when overloaded. Food and water are the main sources of copper intake, however few studies have been conducted to investigate the difference between the ways of its intake in water and food in animals. In this study, copper was fed to mice with food as well as water (two groups: water and diet) for three months at concentrations of 6, 15 and 30 ppm. The copper concentration in water was adjusted for keeping the same amount during its intake in food. The experimental studies show a slow growth rate, lower hepatic reduced glutathione (GSH)/superoxide dismutase (SOD) activity and higher serum 'free' copper in the water group. The brain's soluble amyloid-beta 1-42 (Aβ42) of the water group was significantly higher than that of the diet group at the levels of 6 and 15 ppm. In conclusion, copper in the water group significantly increased the soluble Aβ42 in the brain and the 'free' copper in the serum, decreased the growth rate and hepatic GSH/SOD activity. The research studies carried out suggest that the copper in water is more 'toxic' than copper in diet and may increase the risk of Alzheimer's disease (AD).

Micro determination of plasma and erythrocyte copper by atomic absorption spectrophotometry

PubMed Central

Blomfield, Jeanette; Macmahon, R. A.

1969-01-01

The free and total plasma copper and total erythrocyte copper levels have been determined by simple, yet sensitive and highly specific methods, using atomic absorption spectrophotometry. For total copper determination, the copper was split from its protein combination in plasma or red cells by the action of hydrochloric acid at room temperature. The liberated copper was chelated by ammonium pyrrolidine dithiocarbamate and extracted into n-butyl acetate by shaking and the organic extract was aspirated into the atomic absorption spectrophotometer flame. The entire procedure was carried out in polypropylene centrifuge tubes, capped during shaking. For the free plasma copper measurement the hydrochloric acid step was omitted. Removal of the plasma or erythrocyte proteins was found to be unnecessary, and, in addition, the presence of trichloracetic acid caused an appreciable lowering of absorption. Using a double-beam atomic absorption spectrophotometer and scale expansion × 10, micro methods have been derived for determining the total copper of plasma or erythrocytes with 0·1 ml of sample, and the free copper of plasma with 0·5 ml. The macro plasma copper method requires 2 ml of plasma and is suitable for use with single-beam atomic absorption spectrophotometers. With blood from 50 blood donors, normal ranges of plasma and erythrocyte copper have been determined. PMID:5776543

Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

PubMed

Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

Disinfection of human enteric viruses in water by copper and silver in combination with low levels of chlorine.

PubMed Central

Abad, F X; Pintó, R M; Diez, J M; Bosch, A

1994-01-01

The efficacy of copper and silver ions, in combination with low levels of free chlorine (FC), was evaluated for the disinfection of hepatitis A virus (HAV), human rotavirus (HRV), human adenovirus, and poliovirus (PV) in water. HAV and HRV showed little inactivation in all conditions. PV showed more than a 4 log10 titer reduction in the presence of copper and silver combined with 0.5 mg of FC per liter or in the presence of 1 mg of FC per liter alone. Human adenovirus persisted longer than PV with the same treatments, although it persisted significantly less than HRV or HAV. The addition of 700 micrograms of copper and 70 micrograms of silver per liter did not enhance the inactivation rates after the exposure to 0.5 or 0.2 mg of FC per liter, although on some occasions it produced a level of inactivation similar to that induced by a higher dose of FC alone. Virus aggregates were observed in the presence of copper and silver ions, although not in the presence of FC alone. Our data indicate that the use of copper and silver ions in water systems may not provide a reliable alternative to high levels of FC for the disinfection of viral pathogens. Gene probe-based procedures were not adequate to monitor the presence of infectious HAV after disinfection. PV does not appear to be an adequate model viral strain to be used in disinfection studies. Bacteroides fragilis bacteriophages were consistently more resistant to disinfection than PV, suggesting that they would be more suitable indicators, although they survived significantly less than HAV or HRV. Images PMID:8074518

Investigating relationships between biomarkers of exposure and environmental copper and manganese levels in house dusts from a Portuguese industrial city.

PubMed

Reis, A P; Costa, S; Santos, I; Patinha, C; Noack, Y; Wragg, J; Cave, M; Sousa, A J

2015-08-01

This study reports on data obtained from a pilot survey focusing on house dust and toenail metal(loids) concentrations in residents living in the industrial city of Estarreja. The study design hereby described aims at investigating relationships between human toenails and both copper and manganese levels in settled house dusts. A total of 21 households and 30 individuals were recruited for the pilot study: 19 households corresponding to 27 residents living near the industrial complex, forming the exposed group, plus 2 households and 3 residents from residential areas with no anticipated environmental contaminants that were used for comparison. Factorial analysis was used for source identification purposes. Investigation on the potential influence of environmental factors over copper and manganese levels in the toenails was carried out via questionnaire data and multiple correspondence analysis. The results show that copper concentrations are more elevated in the indoor dusts, while manganese concentrations are more elevated in the outdoor dust samples. The geometrical relationships in the datasets suggest that the backyard soil is a probable source of manganese to the indoor dust. Copper and manganese contents in the toenail clippings are more elevated in children than in adults, but the difference between the two age groups is not statistically significant (p > 0.05). Investigation of environmental factors influencing the exposure-biomarker association indicates a probable relationship between manganese contents in indoor dust and manganese levels in toenail clippings, a result that is partially supported by the bioaccessibility estimates. However, for copper, no relationship was found between indoor dusts and the biomarkers of exposure.

Background studies in support of a feasibility assessment on the use of copper-base materials for nuclear waste packages in a repository in tuff

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Konynenburg, R.A.; Kundig, K.J.A.; Lyman, W.S.

1990-06-01

This report combines six work units performed in FY`85--86 by the Copper Development Association and the International Copper Research Association under contract with the University of California. The work includes literature surveys and state-of-the-art summaries on several considerations influencing the feasibility of the use of copper-base materials for fabricating high-level nuclear waste packages for the proposed repository in tuff rock at Yucca Mountain, Nevada. The general conclusion from this work was that copper-base materials are viable candidates for inclusion in the materials selection process for this application. 55 refs., 48 figs., 22 tabs.

Protective effect of selenium on lung cancer in smelter workers.

PubMed Central

Gerhardsson, L; Brune, D; Nordberg, I G; Wester, P O

1985-01-01

A possible protective effect of selenium against lung cancer has been indicated in recent studies. Workers in copper smelters are exposed to a combination of airborne selenium and carcinogens. In this study lung tissue concentrations of selenium, antimony, arsenic, cadmium, chromium, cobalt, lanthanum, and lead from 76 dead copper smelter workers were compared with those of 15 controls from a rural area and 10 controls from an urban area. The mean exposure time for the dead workers was 31.2 years, and the mean retirement time after the end of exposure 7.2 years. Lung cancer appeared in the workers with the lowest selenium lung tissue levels (selenium median value 71 micrograms/kg wet weight), as compared with both the controls (rural group, median value 110; urban group, median value 136) and other causes of death among the workers (median value 158). The quotient between the metals and selenium was used for comparison: a high quotient indicating a low protective effect of selenium and vice versa. The median values of the quotients between antimony, arsenic, cadmium, lanthanum, lead, chromium, and cobalt versus selenium were all numerically higher among the cases of lung cancer, the first five significantly higher (p less than 0.05) in 28 of the 35 comparisons between the lung cancer group and all other groups of smelter workers and controls. The different lung metal concentrations for each person were weighted according to their carcinogenic potency (Crx4 + Asx3 + Cdx2 + Sbx1 + Cox1 + Lax1 + Pbx1) against their corresponding selenium concentrations. From these calculations the protective effect of selenium was even more pronounced. PMID:4041390

A preliminary study of preservative retention and penetration in ACQ-treated timbers using near infrared spectroscopy

Treesearch

Chi-Leung So; Thomas L. Eberhardt; Stan T. Lebow; Leslie H. Groom

2006-01-01

Near infrared (NIR) spectroscopy has been previously used in our laboratory to predict copper, chromium, and arsenic levels in samples of chromated copper arsenate (CCA)-treated wood. In the present study, we utilized our custom-made NIR scanning system, NIRVANA (near infrared visual and automated numerical analysis), to scan cross sections of ACQ (alkaline copper quat...

Copper Deficiency in Calves in Northcentral Manitoba

PubMed Central

Smart, M. E.; Gudmundson, J.; Brockman, R. P.; Cymbaluk, N.; Doige, C.

1980-01-01

Four seven month old Simmental calves were examined because of unthriftiness, a persistent cough, stiffness and lameness. The calves had gastrointestinal and pulmonary parasitism. Analysis of the blood copper levels of these calves and of cows and calves on the farm indicated a generalized deficiency. Only the calves affected with parasitism showed signs of clinical copper deficiency. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:7260830

Trace copper measurements and electrical effects in LPE HgCdTe

NASA Astrophysics Data System (ADS)

Tower, J. P.; Tobin, S. P.; Norton, P. W.; Bollong, A. B.; Socha, A.; Tregilgas, J. H.; Ard, C. K.; Arlinghaus, H. F.

1996-08-01

Recent improvements in sputter initiated resonance ionization spectroscopy (SIRIS) have now made it possible to measure copper in HgCdTe films into the low 1013 cm-3 range. We have used this technique to show that copper is responsible for type conversion in n-type HgCdTe films. Good n-type LPE films were found to have less than 1 x 1014 cm-3 copper, while converted p-type samples were found to have copper concentrations approximately equal to the hole concentrations. Some compensated n-type samples with low mobilities have copper concentrations too low to account for the amount of compensation and the presence of a deep acceptor level is suggested. In order to study diffusion of copper from substrates into LPE layers, a CdTe boule was grown intentionally spiked with copper at approximately 3 x 1016 cm-3. Annealing HgCdTe films at 360°C was found to greatly increase the amount of copper that diffuses out of the substrates and a substrate screening technique was developed based on this phenomenon. SIRIS depth profiles showed much greater copper in HgCdTe films than in the substrates, indicating that copper is preferentially attracted to HgCdTe over Cd(Zn)Te. SIRIS spatial mapping showed that copper is concentrated in substrate tellurium inclusions 5 25 times greater than in the surrounding CdZnTe matrix.

N Deposition Effects on Hermes Copper Butterfly (Lycaena hermes) Habitat in Southern California

NASA Astrophysics Data System (ADS)

Malter, L. I.; Vourlitis, G. L.

2017-12-01

Atmospheric nitrogen (N) deposition has become a global concern over the past few decades as population sizes have increased. San Diego County, CA, USA, with a high population density, Mediterranean-type climate, and high biodiversity, is an ideal site for an extensive N deposition study. Chronic anthropogenic N deposition is one of the main contributing factors to affect plant species diversity (Vourlitis and Pasquini 2009) and invasive species encroachment (Minnich and Dezzani 1998). It is also the location of the rare endemic Hermes copper butterfly (Lycaena hermes), which has received minimal research and remains a mystery to many ecologists. We hypothesized that N deposition will impact Hermes abundance; however, there is limited research on the effects of N deposition on butterfly habitat. Thus, this study aims to determine the effect of increased N on the alterations to plant-insect interactions. These effects are being measured at five sites throughout San Diego County in current or historical Hermes copper habitat. N deposition collectors have been placed under the canopy of spiny redberry shrubs (Rhamnus crocea) to accumulate N throughfall at each site. Soil and redberry stem fragments are being used to analyze total N and Carbon (C), water potential, and shrub growth throughout the course of this study. Despite the preliminary nature of our results, we show a number of trends between data groups, such as large differences in soil and tissue N and C between the study sites, suggesting differences in atmospheric N inputs. These variations in soil N availability lead to variations in leaf tissue chemistry, which can ultimately impact the performance of the Hermes copper larvae. Our current data demonstrate some clear trends, but whether these trends remain consistent and interpretable remains to be seen. We anticipate this research will increase our understanding of spatial variation patterns of N deposition in southern California and how that N input might affect the rare Hermes copper butterfly and its host plant, Rhamnus crocea. Furthermore, these data are important because they might help us understand why Hermes is in decline and which sites should be prioritized for management.

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

Multi-Copper Oxidases and Human Iron Metabolism

PubMed Central

Vashchenko, Ganna; MacGillivray, Ross T. A.

2013-01-01

Multi-copper oxidases (MCOs) are a small group of enzymes that oxidize their substrate with the concomitant reduction of dioxygen to two water molecules. Generally, multi-copper oxidases are promiscuous with regards to their reducing substrates and are capable of performing various functions in different species. To date, three multi-copper oxidases have been detected in humans—ceruloplasmin, hephaestin and zyklopen. Each of these enzymes has a high specificity towards iron with the resulting ferroxidase activity being associated with ferroportin, the only known iron exporter protein in humans. Ferroportin exports iron as Fe2+, but transferrin, the major iron transporter protein of blood, can bind only Fe3+ effectively. Iron oxidation in enterocytes is mediated mainly by hephaestin thus allowing dietary iron to enter the bloodstream. Zyklopen is involved in iron efflux from placental trophoblasts during iron transfer from mother to fetus. Release of iron from the liver relies on ferroportin and the ferroxidase activity of ceruloplasmin which is found in blood in a soluble form. Ceruloplasmin, hephaestin and zyklopen show distinctive expression patterns and have unique mechanisms for regulating their expression. These features of human multi-copper ferroxidases can serve as a basis for the precise control of iron efflux in different tissues. In this manuscript, we review the biochemical and biological properties of the three human MCOs and discuss their potential roles in human iron homeostasis. PMID:23807651

Genetic Dissection of Nutritional Copper Signaling in Chlamydomonas Distinguishes Regulatory and Target Genes

PubMed Central

Eriksson, Mats; Moseley, Jeffrey L.; Tottey, Stephen; del Campo, Jose A.; Quinn, Jeanette; Kim, Youngbae; Merchant, Sabeeha

2004-01-01

A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2 (CRD2), distinguished as regulatory or target genes on the basis of phenotype. CRR1 was shown previously to be required for transcriptional activation of target genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c6 (which is a heme-containing substitute for copper-containing plastocyanin), coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase. We show here that CRR1 is required also for normal accumulation of copper proteins like plastocyanin and ferroxidase in copper-replete medium and for apoplastocyanin degradation in copper-deficient medium, indicating that a single pathway controls nutritional copper homeostasis at multiple levels. CRR1 is linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a gain-of-function mutation resulting in copper-independent expression of CYC6. CRR1 is required also for hypoxic growth, pointing to a physiologically meaningful regulatory connection between copper deficiency and hypoxia. The growth phenotype of crr1 strains results primarily from secondary iron deficiency owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper distribution to a multicopper ferroxidase involved in iron assimilation. Mutations at the CRD2 locus also result in copper-conditional iron deficiency, which is consistent with a function for CRD2 in a pathway for copper delivery to the ferroxidase. Taken together, the observations argue for a specialized copper-deficiency adaptation for iron uptake in Chlamydomonas. PMID:15514054

Testicular toxicity and sperm quality following copper exposure in Wistar albino rats: ameliorative potentials of L-carnitine.

PubMed

Khushboo, Maurya; Murthy, Meesala Krishna; Devi, Maibam Sunita; Sanjeev, Sanasam; Ibrahim, Kalibulla Syed; Kumar, Nachimuthu Senthil; Roy, Vikas Kumar; Gurusubramanian, Guruswami

2018-01-01

Copper is a persistent toxic and bio-accumulative heavy metal of global concern. Continuous exposure of copper compounds of different origin is the most common form of copper poisoning and in turn adversely altering testis morphology and function and affecting sperm quality. L-carnitine has a vital role in the spermatogenesis, physiology of sperm, sperm production and quality. This study was designed to examine whether the detrimental effects of long-term copper consumption on sperm quality and testis function of Wistar albino rat could be prevented by L-carnitine therapy. The parameters included were sperm quality (concentration, viability, motility, and morphology), histopathology, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum urea, serum creatinine, serum testosterone and testis antioxidant enzyme levels (superoxide dismutase and glutathione-S-transferase), and biomarkers of oxidative stress (lipid peroxidation and expression of heat shock protein 70 in testis). Three-month-old male Wistar rats (n = 30) were divided into six groups as group 1 (G1, 0.9% saline control), group 2 (G2, CuSO4 200 mg/kg dissolved in 0.9% saline water), groups 3 and 4 (G3 and G4, L-carnitine 50 and 100 mg/kg dissolved in 0.9% saline water, respectively), and groups 5 and 6 (G5 and G6, CuSO 4 200 mg/kg plus L-carnitine, 50 and 100 mg/kg dissolved in 0.9% saline water, respectively). Doses of copper (200 mg/kg) and L-carnitine (50 and 100 mg/kg) alone and in combinations along with untreated control were administered orally for 30 days. The following morphological, physiological, and biochemical alterations were observed due to chronic exposure of copper (200 mg/kg) to rats in comparison with the untreated control: (1) generation of oxidative stress through rise in testis lipid peroxidation (12.21 vs 3.5 nmol MDA equivalents/mg protein) and upregulation of heat shock protein (overexpression of HSP70 in testis), (2) liver and kidney dysfunction [elevation in serum ALT (81.65 vs 48.08 IU/L), AST (156.82 vs 88.25 IU/L), ALP (230.54 vs 148.16 IU/L), urea (12.65 vs 7.45 mmol/L), and creatinine (80.61 vs 48.25 μmol/L) levels], (3) significant decrease in body (99.64 vs 106.09 g) and organ weights (liver-3.48 vs 4.99 g; kidney-429.29 vs 474.78 mg; testes-0.58 vs 0.96 g), (4) imbalance in hormonal and antioxidant enzyme concentrations [significant decline in serum testosterone (0.778 vs 3.226 ng/mL), superoxide dismutase (3.07 vs 8.55 μmol/mg protein), and glutathione-S-transferase (59.28 vs 115.58 nmol/mg protein) levels], (5) severe alterations in the testis histomorphology [sloughed cells (90.65%, score 4 vs 15.65%, score 1), vacuolization (85.95%, score 4 vs 11.45%, score 1), cellular debris along with degenerative characteristics, accentuated germ cell depletion in the seminiferous epithelium, severe damage of spermatogonia and Sertoli cells (73.56%, score 3 vs 0%, score 1)], (6) suppression of spermatogenic process [hypospermatogenesis (low Jhonsen testicular biopsy score 4 vs 9.5), decrease in tubules size (283.75 vs 321.25 μm in diameter), and no. of germ cells (81.8 vs 148.7/100 tubules), Leydig cells (5.2 vs 36.65/100 tubules), and Sertoli cells (8.1 vs 13.5/100 tubules)], (7) sperm transit time was shorter in caput and cauda and ensued in incomplete spermatogenic process and formation of immature sperm leading to infertility, (8) sperm quality was affected significantly [decreased daily sperm production (13.21 vs 26.9 × 10 6 sperms/mL), sperm count (96.12 vs 154.25 × 10 6 /g), sperm viability (26.88 vs 91.65%), and sperm motility (38.48 vs 64.36%)], and (9) increase of head (32.82 vs 2.01%) and tail (14.85 vs 0.14%) morphologic abnormalities and DNA fragmentation index (88.37 vs 11.11%). Oxidative stress and their related events appear to be a potential mechanism involved in copper testicular toxicity and L-carnitine supplementation significantly modulated the possible adverse effects of copper on seminiferous tubules damage, testes function, spermatogenesis, and sperm quality. It was validated that the use of L-carnitine at doses of 50 and 100 mg/kg protects against copper-induced testicular tissue damage and acts as a therapeutic agent for copper heavy metal toxicity.

Evolution of a Heavy Metal Homeostasis/Resistance Island Reflects Increasing Copper Stress in Enterobacteria

PubMed Central

Staehlin, Benjamin M.; Gibbons, John G.; Rokas, Antonis; O’Halloran, Thomas V.; Slot, Jason C.

2016-01-01

Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including the cus (copper sensing copper efflux system), and pco (plasmid-borne copper resistance system) systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest that CHASRI originated in a relative of Enterobacter cloacae as the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer within Enterobacteriaceae and also to certain members of Shewanellaceae, where the original pco module was replaced by a divergent pco homolog. Analyses of copper stress mitigation suggest that CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens. PMID:26893455