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Effect of a combination of copper and hexetidine on the acidogenicity and copper accumulation in dental plaque in vivo.

A double-blind crossover study on 4 adult volunteers was performed to evaluate the effect of hexetidine on Cu2+ accumulation in dental plaque as well as a possible enhanced effect of copper on inhibition of acid production in the presence of hexetidine. The experimental period was 5 days. No oral hygiene was allowed, and sucrose-containing chewing gum was used to enhance plaque formation during the test period. In order to evaluate the effect on pH, the test persons rinsed with a 15% glucose (w/v) solution on the 5th experimental day. Plaque pH values recorded before and 5 min after the rinse served as control values. One hour later the test persons rinsed with 10 ml of the test solutions for 1 min. Glucose rinses with pH measurements 5 min after the rinse were carried out 0, 3, and 7 h after the test agents were used. The combination of 1.0 mM copper and 2.0 mM hexetidine gave a significant (p less than 0.05) inhibition of acid production at all times compared both to the controls and to each of the test agents separately. Plaque samples were collected with a toothpick immediately before a 1-min rinse with 10 ml of the test solutions. Subsequent plaque samples were taken 5 min and 3 and 8 h after a rinse from corresponding tooth surfaces. Dry weight was estimated, the plaque bacteria digested by HNO3, and the amount of Cu2+ determined by atomic absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗

Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc.

BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn.

Animals↗

[In vivo toxicity, lipid peroxide lowering, and glutathione, ascorbic acid and copper elevation induced in mouse liver by low dose of oxine-copper, a fungicide].

While oxine-copper (OxCu) is generally used as an agricultural fungicide and induces a harmful effect on ecosystems, little information is available regarding a toxic effect of OxCu on mammals. In this article, we examined in vivo induction of toxicity and change of levels of glutathione and ascorbic acid, major biological antioxidants, lipid peroxide and copper (Cu) in liver and kidney 4 h and 24 h after intraperitoneal administration of OxCu at a low dose (0.05 mmol/kg) to mice. Increased hepatic ascorbic acid and Cu levels were found at 4 h after the treatment. In addition, body weight change was lowered and serum glutamic pyruvic transaminase activity was elevated significantly compared to control at 24 h after the treatment, suggesting induction of systemic and hepatic toxicity respectively. These were accompanied by lowered lipid peroxide level and enhanced glutathione, ascorbic acid and Cu levels in the mouse liver. On the other hand, OxCu induced no elevation in serum urea nitrogen concentration 4 h and 24 h after the treatment, suggesting no induction of nephrotoxicity, accompanied by no change in renal lipid peroxide, glutathione, ascorbic acid and Cu levels. These results suggest that hepatic Cu elevation may induce hepatotoxicity and no renal Cu elevation may lead to no induction of nephrotoxicity after the treatment with OxCu.

Animals↗

[In vivo toxicity, and glutathione, ascorbic acid and copper level changes induced in mouse liver and kidney by copper(II) gluconate, a nutrient supplement].

While copper(II) gluconate (CuGL) is generally used as a nutrient supplement for infant foods and as an oral deodorant, little information is available regarding a toxic effect of CuGL on mammals. In this article, we examined in vivo induction of toxicity and change of level of glutathione and ascorbic acid, major biological antioxidants, lipid peroxide and copper (Cu) in liver and kidney 4 h after single intraperitoneal administration of CuGL at 0.05 and 0.10 mmol/kg to mice. Serum glutamic pyruvic transaminase (SGPT) activity, an indicator of hepatotoxicity, significantly increased compared to control in proportion to doses of CuGL. Hepatic level of glutathione measured as nonprotein sulfhydryl was not proportional to CuGL doses, but enhanced after dosing of 0.05 mmol/kg and lowered by 0.10 mmol/kg. Like SGPT activity, serum urea nitrogen (SUN) concentration, an indicator of nephrotoxicity, significantly increased in proportion to doses of CuGL. Renal glutathione level was not different from control after dosing of 0.05 mmol/kg and lowered by 0.10 mmol/kg. In both organs, relative organ weight and lipid peroxide level were not affected by the treatment with CuGL; ascorbic acid level was elevated after dosing of 0.05 mmol/kg and was not different from control after treatment with 0.10 mmol/kg; like SGPT activity and SUN concentration, Cu level significantly increased in proportion to doses of CuGL. These results suggest that in the liver and kidney after the treatment with CuGL Cu accumulated may induce toxicity, leading to level changes of glutathione and ascorbic acid and to no induction of oxidative damage.

Animals↗

Long-term effects of consumption of low-copper diets with or without supplemental molybdenum on copper status, performance, and carcass characteristics of cattle.

We used 42 Angus bull calves (7 mo of age) to determine long-term effects of low Cu diets with or without supplemental Mo on performance, carcass characteristics, and Cu status. Twenty-two bulls were injected with 90 mg of Cu 28 d before weaning. After weaning, injected steers were fed a diet supplemented with 7.5 mg of Cu/kg of DM; control steers received no supplemental Cu. At the end of the 40-d receiving phase, supplemental Cu was reduced to 5 mg/kg of DM. One half of the steers in each group were fed 5 mg of supplemental Mo/kg of DM following the receiving phase. The growing phase lasted 196 d. Steers were then switched to a high concentrate finishing diet for 49 d. Copper injection increased (P < .01) plasma Cu concentrations at weaning, and Cu-supplemented steers had greater (P < .05) plasma Cu, ceruloplasmin, superoxide dismutase activity (SOD), and liver Cu at the beginning of the growing phase. Supplemental Mo depressed plasma Cu, ceruloplasmin, and SOD during the growing and finishing phases in non-Cu-supplemented but not in Cu-supplemented steers. Copper supplementation increased DMI during the receiving (P < .05) and growing (P < .08) phases and increased (P < .08) ADG and gain:feed ratios during the finishing phase. Steers fed supplemental Cu produced carcasses with less (P < .06) backfat and slightly larger (P < .09) rib eye areas. The results of this experiment suggest that dietary Cu concentrations may alter cattle performance and carcass characteristics.

Abattoirs↗

Effects of copper deficiency and copper deficiency coupled with high dietary iron or molybdenum on phagocytic cell function and response of calves to a respiratory disease challenge.

A study was conducted to determine the effects of supplementing a diet marginally deficient in copper (Cu) with iron (Fe), molybdenum (Mo), or Cu on phagocytic cell function and disease resistance of calves. Thirty-one calves were born to heifers fed a corn silage-based diet containing 4.5 mg of Cu/kg. Treatments consisted of 1) control (CON; no supplemental Cu, Fe, or Mo), 2) 600 mg of Fe added/kg (FE), 3) 5 mg of Mo added/kg (MO), or 4) 10 mg of Cu added/kg of DM (CU). Activity of superoxide dismutase was lower (P < .06) in neutrophils from MO vs CON or CU calves at 170 d of age. bactericidal activity of neutrophils from MO calves tended (P = .15) to be lower compared with those from CU calves at 70 d of age. Calves were inoculated intranasally with live infectious bovine rhinotracheitis virus (IBRV) 2 d after weaning, followed by intratracheal administration of Pasteurella hemolytica 5 d later. Iron- and Cu-supplemented calves exhibited higher (P < .01) body temperatures and lower (P < .06) feed intakes following IBRV inoculation compared with CON and MO calves. Copper-supplemented calves had higher levels of plasma tumor necrosis factor (TNF) than MO calves at weaning (P < .05) and tended to have higher plasma TNF (P = .11) than FE and MO calves 5 d after IBRV inoculation. These data indicate that dietary levels of Mo and Cu can affect body temperature and feed intake responses to disease by affecting TNF and perhaps other cytokines.

Aging↗

Inhibition of iron and copper uptake by iron, copper and zinc.

Interactions of micronutrients can affect absorption and bioavailability of other nutrients by a number of mechanisms. In aqueous solutions, and at higher uptake levels, competition between elements with similar chemical characteristics and uptake process can take place. The consequences of these interactions may depend on the relative concentrations of the nutrients. In this work, we measure the effects of increasing concentrations of iron, zinc, and copper on iron and copper uptake in Caco-2 cells. Intracellular Fe or Cu levels were affected by incubating with increased concentrations of metals. However, when the cells already had different intracellular metal concentration, the uptake of Fe or Cu was nor affected. In competition studies, we showed that Cu and Zn inhibited Fe uptake, and while Fe inhibited Cu uptake, Zn did not. When the three metals were given together (1:1:1 ratio), Fe or Cu uptake was inhibited approximately 40%. These results point to a potential risk in the absorption and bioavailability of these minerals by the presence of other minerals in the diet. This aspect must be considered in food supplementation and fortification programs.

Biological Transport↗

The influence of amino acid side chains on water binding to the copper(II) in bis(N,N-dimethyl-L-alpha-isoleucinato)-copper(II): an EPR and molecular mechanics study.

Simulations were done of the electron paramagnetic resonance (EPR) spectra for bis(N,N-dimethyl-L-alpha-isoleucinato)copper(II) dissolved in deuterated methanol as a function of temperature. They indicated different behaviour of the complex below and above 300 degrees K. The effect was examined by the conformational analysis of the copper(II) complex with a new molecular mechanics force field.

Amino Acids↗

Removal of copper by Pseudomonas putida strain S4 isolated from copper mines.

A bacterial strain, Pseudomonas putida S4, was isolated from smelter drainage of copper mines. The strain exhibited resistance to several heavy metals, like aluminium (Al), zinc (Zn), nickel (Ni), cobalt (Co) besides copper (Cu). Strain S4 could accumulate Cu from the Cu-supplemented growth medium. In the present study, we have demonstrated the Cu2+ removal capacity of this strain from various samples such as mine effluent, low-grade ore and ore-tailings, collected from the mining site. Moreover, approximately 80% of the accumulated Cu2+ could be recovered from the loaded biomass by a simple desorption procedure.

Biodegradation, Environmental↗

In vivo comparison of copper blood-pool agents: potential radiopharmaceuticals for use with copper-62.

Two techniques for labeling of albumin with copper-67 (67Cu) and 62Cu were investigated; one using the native Cu(II) binding site of the protein and the other employing a bifunctional chelate, 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane- N,N'N",N"'-tetraacetic acid (Br-benzyl-TETA or BAT), conjugated to the protein. Rat biodistribution experiments with 67Cu demonstrated retention of i.v. 67Cu-benzyl-TETA-albumin in the blood pool identical to co-injected 125I-albumin. By contrast, i.v. administration of either [67Cu]-Cu-acetate or [67Cu]-Cu-acetate pre-mixed with albumin results in relatively rapid clearance of blood-pool radioactivity as the tracer is excreted into the urine. The 62Cu-benzyl-TETA-albumin radiopharmaceutical was obtained in ca. 17% radiochemical yield (end of synthesis, without decay correction) following a procedure that can be completed in 15-18 min. In PET experiments with a baboon, myocardial blood volume images with 62Cu-benzyl-TETA-albumin were identical to those obtained with C15O. Use of the 62Cu-benzyl-TETA-albumin image for blood-pool subtraction of a 62Cu-PTSM myocardial perfusion image is illustrated. Copper-62-benzyl-TETA-HSA should be a useful, generator-produced radiotracer for the detection of the vascular pool at PET facilities without cyclotrons.

Animals↗

Ovine white-liver disease (OWLD). Serum copper and effects of copper and selenium supplementation.

Serum copper was generally higher in lambs affected with ovine white-liver disease (OWLD) than in cobalt/vitamin B12 supplemented lambs grazing the same pastures. Although the copper content of the grass was very low on the OWLD pastures, dosing lambs with Cu alone resulted in worsening of the clinical condition and aggravation of clinical pathology. Dosing with selenium had no effect on OWLD. Dosing with a combination of Co, Se and Cu resulted in normal lamb growth and normal laboratory tests. Lambs growing well on other pastures (H) showed elevated serum Cu when they were subclinically B12 deficient.

Animals↗

Effects of selenium and copper administration on blood selenium and copper profile of cattle.

Forty yearling shorthorn heifers were winter-fed barley silage, a diet low in copper and selenium. The animals were divided into 4 groups of 10 animals each. One group was unsupplemented, while other treatments were copper (Cu), selenium (Se), or combined Cu-Se administered by subcutaneous injections. Low Cu and Se concentrations were observed in the blood plasma of the unsupplemented group. The administration of Cu and Se raised the blood plasma Cu and Se concentrations in the heifers. However, Cu or Se administration had no effect on the growth of heifers and there was no interaction between the Se and Cu treatments.

Animals↗

An assessment of the toxicity of parenteral treatment with copper EDTA and copper heptonate in sheep.

The toxicity of 2 parenteral copper (Cu) supplements was investigated. Di-sodium copper ethylene diamino tetra acetate (Cu EDTA) and Cu heptonate were administered to sheep (n = 9) by a single subcutaneous injection at a concentration of 0,2, 1 and 2 mg Cu/kg each (Trial 1.) Nine sheep were untreated and served as controls. The same treatments were applied to 2 sheep each (Trial 2) with the addition of 3 mg Cu/kg live body mass as Cu heptonate, and Cu heptonate administered intravenously at rates of 0,2, 0,4 and 0,6 mg Cu/kg live body mass. In Trial 1, 67% of the sheep treated with Cu EDTA at 2 mg Cu/kg live body mass died within 3 to 17 d after treatment, while no mortalities occurred in sheep where Cu heptonate was administered at the same dosage rate and even at 3 mg Cu/kg live body mass (P < or = 0,01). Post-mortem examination suggested acute Cu toxicity in all cases. Liver Cu concentrations were markedly increased (P < or = 0,05) by both supplements in groups of 3 treated sheep slaughtered over a 3-month period compared to control animals. The liver Cu concentrations of sheep that succumbed to Cu toxicity were within the normal range of 100 to 450 mg/kg DM. Results from Trial 2 suggested that the 2 sheep treated with 2 mg Cu/kg live body mass as Cu EDTA, experienced a haemolytic crisis between 5 and 11 d after treatment, resulting in the death of one of these sheep. The haemolytic crisis was characterised by a severe decrease in haemoglobin concentration and haematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The levels of cadmium, zinc and copper in the renal cortex and liver of the inhabitants of the copper basin.

Tissues were analysed from 60 subjects deceased at the age of 18-82 (mean 49 years), inhabitants of the southwestern region of Poland (Legnica Copper Basin). Mean cadmium, zinc and copper concentrations determined by flame AAS were for renal cortex 41.8; 47.8 and 2.3 micrograms Me/g tissue, respectively. The respective levels in the liver were 2.3; 51.6 and 4.6 micrograms Me/g tissue (w.w.). A broad range of cadmium levels was found in renal cortex (4.2-129.3.micrograms/g), with the highest values in the 40-60 age group. The effect of tobacco smoking is more evident than in other countries: 26.3 micrograms/g in non-smokers vs. 54.6 micrograms/g in smokers. Similar proportions were found by computing the whole body burden of cadmium. Compared with other regions of Poland the environmental exposure of humans to cadmium is moderate, however, it is higher than in other European countries.

Adolescent↗

Serum and endometrial copper, zinc, iron and cobalt with inert and copper-containing IUCDs.

Serum and endometrial copper (Cu), zinc (Zn), iron (Fe) and serum cobalt (Co) were measured in the mid-follicular and mid-luteal phases of the menstrual cycles in 30 Lippes loops users, 30 CuT-200 IUCD users and 24 matched controls by atomic absorption spectrophotometry. In the control group, there was no statistically significant difference in mean mid-luteal, compared to mid-follicular, levels of serum Cu, Zn, Fe and Co and endometrial Zn. Mid-luteal endometrium contained significantly higher mean Cu, and lower mean Fe levels. In Lippes loop users, compared to controls, the only statistically significant differences were lower mean mid-follicular serum Zn, lower mean endometrial Zn and Fe, and higher mean mid-luteal endometrial Fe. In CuT-200 users, compared to controls, there was significantly higher mean mid-follicular serum Zn and lower mean mid-luteal serum Co, higher mean mid-follicular endometrial Cu and lower mean mid-follicular endometrial Fe levels. Compared to Lippes loop, CuT-200 users had significantly higher mean mid-follicular serum Co and endometrial Cu and Zn, and lower mean mid-follicular endometrial Fe.

Adult↗

Concentrations of copper in human secretions and weight of the copper wire during the 4 to 7 years after insertion of a Cu-IUD (intrauterine device).

The useful life span of the two most commonly used copper intrauterine devices (Cu-IUDs) (Gravigard and Cu-T) was investigated in a long-term study up to 90 months after insertion. Minor differences between the two types of devices were found that, however, probably do not contribute to a diverging contraceptive efficacy with time. To be able to ensure maximal contraceptive effect, the authors suggest on the basis of the present data that the time of use not exceed 5 to 6 years.

Adolescent↗