Cu In Plasma Research Articles

The effects of copper status on thiamine metabolism in sheep fed a high sulfur diet

The effect of Cu status on selected aspects of thiamine metabolism was studied in sheep exposed to high dietary S over a period of 14 wk. Nine cross-bred 2-mo-old female lambs were used. The animals were divided into three groups (n = 3) and offered a basal diet containing 0.63% S (0.45% as sulfate) and 14 mg thiamine kg−1 DM. Copper and Mo were variable ingredients. Sheep in group 1 received a 14 mg Cu kg−1 DM diet, whereas those in groups 2 and 3 received a 6 mg Cu kg−1 DM diet. To precipitate Cu insufficiency, group 3 received an additional 20 mg Mo kg−1 DM diet. The concentration of blood thiamine tended to increase in sheep from group 1, but decline in sheep from group 3 which also had a lower concentration of Cu in plasma. In these groups, a similar trend was observed in thiamine and Cu concentrations of duodenal fluid. Liver thiamine tended to be higher (P = 0.09) in group 3 sheep than in group 1 and 2 sheep. However, the concentration of thiamine in the kidney and cerebral cortex did not differ among the groups. Copper concentration was lowest in the liver and brain, but highest in the kidney of sheep from group 3. The erythrocyte thiamine pyrophosphate (TPP) effect increased (P < 0.035) in sheep in groups 2 and 3 during the 8th week on the diet and in all sheep during the 13th week. We conclude that Cu plays an important role in the metabolism of thiamine in the gastrointestinal tract, as well as systemically. Key words: Sulfur, molybdenum, copper, thiamine, interactions, sheep

A kinetic model of copper metabolism in lactating dairy cows

A model of Cu metabolism in dairy cows was developed using a stable isotope, Cu-65, as an in vivo tracer. Copper-65 was administered intravenously to six dairy cows fed a diet of corn silage plus grain concentrate containing 10 mg Cu, 1.1 mg Mo and 2.2 g S kg−1 diet dry matter. The distribution of tracer and the natural concentration of Cu in liver, plasma and milk were monitored for 140 d (urine and feces for 5 and 7 d). A kinetic modeling program (SAAM/CONSAM) was utilized for development of the model. Seven compartments, including liver, two plasma compartments, remaining body, gut, milk (including udder) and feces were required to describe the experimental data. The model included five routes of Cu loss: biliary and nonbiliary fecal excretion, urinary excretion and two routes into the milk/udder compartment. The solution to the model indicated that 5.1 ± 1.5% (mean ± SD, n = 6) of dietary Cu was absorbed from the gut; 92.2 ± 5.0% of the absorbed Cu was removed directly by liver; 38.4 ± 13.3% of Cu leaving the liver entered the nondirect-reacting (NDR) Cu compartment of plasma; 80.7 ± 9.0% of NDR Cu entered the remaining body compartment while the balance of the NDR Cu supplied the milk/udder compartment. The transfer of Cu from liver to the NDR Cu in plasma appeared to be a point of metabolic control in Cu metabolism, and was represented in the model by an empirical nonlinear function. Key words: Copper, dairy, cow, modeling, isotope, metabolism

COMPARISON OF COPPER SULFATE AND COPPER PROTEINATE AS COPPER SOURCES FOR COPPER-DEPLETED STEERS FED HIGH MOLYBDENUM DIETS

Copper (Cu) depleted steers were used to compare copper sulfate and copper proteinate as Cu sources for cattle consuming high molybdenum diets. Two experiments utilizing corn silage and barley concentrate diets with 10 mg added Mo kg−1 DM were undertaken. Experiment A was a 105-d study in which an 83:17 ratio of silage to concentrate was fed, whereas, experiment B was an 84-d study comparing the same Cu treatments for cattle fed a 26:74 (Low) or a 64:36 (High) ratio of silage to concentrate. Cu treatments for both experiments were: no supplemental Cu (0Cu); a dietary supplement of 10 mg Cu kg−1 DM added as copper sulfate (CuSO); and a dietary supplement of 10 mg Cu kg−1 DM added as copper proteinate (CuPro). Both Cu supplements improved (P < 0.05) concentrations of Cu in plasma for both experiments and improved (P < 0.05) concentration of Cu in liver for experiment B. Copper supplementation (P < 0.05) reduced plasma Mo concentrations in experiment A relative to animals receiving no supplemental Cu. Both Cu sources resulted in reduced rumen fluid soluble Mo concentrations. Steers in experiment A had lower initial liver and plasma Cu concentrations than was observed for experiment B. Average daily gains for steers consuming CuPro were 16.8% greater (P < 0.05) than for 0Cu with CuSO being intermediate for experiment A. Results indicate that the bioavailability of Cu from Cu proteinate is similar to that of copper sulfate in-Cu depleted steers consuming diets containing excess Mo. Key words: Cattle, copper sulfate, copper proteinate, copper, molybdenum

THE EFFECTS OF CAPTOPRIL AND ENALAPRIL ON TISSUE LEVELS OF VARIOUS ELEMENTS IN SPONTANEOUSLY HYPERTENSIVE RATS

The effects of two inhibitors of angiotensin I converting enzyme, captopril and enalapril, on the concentrations of Na, K, Ca, Mg, Fe, S, P, Sr, Mn, Cu and Zn ions in blood, plasma, heart, skeletal muscle, liver and kidney of spontaneously hypertensive rats (SHR) were studied. Captopril and enalapril were given by the intraperitoneal route for 15 days, at 160 mumols/kg/d and 40 mumols/kg/d, respectively. Elements in tissues were determined by inductively coupled plasma emission spectrometry with a JY 48 instrument. The common changes produced with the two drugs were: a decrease of Na in muscle (-10%), a decrease of Ca in plasma and kidney (less than -10%) and a decrease of Mn in liver (-15%). The main effects observed with only one of the two drugs were: an increase of Cu in plasma (+26%) with captopril, and increases of Sr in heart (+56%), muscle (+79%) and liver (+74%) with enalapril. Zinc concentration in tissues was not modified, except for an increase in liver with captopril (+13%) and a decrease in heart with enalapril (-11%).

The effects of supplementation of the diet of young steers with Mo and S on the intracellular distribution of copper in liver and on copper fractions in blood

Young Jersey steers weighing between 100 and 200 kg were fed a basic diet supplemented with Mo, 35 ppm, and S, 0·3% of dry matter intake, for 24 weeks. Total liver copper levels, assessed from biopsy material, fell more rapidly than those of a control group fed the basic diet. While the copper levels declined in all the subcellular fractions examined, that is nuclear, mitochondrial and cytosol; the decrease was most marked in the nuclear fraction. Moderate supplementation (5 ppm Cu) of the controls increased liver copper values, particularly in the nuclear fraction. Total plasma copper levels rose initially in the Mo and S supplemented animals, but the most striking feature was the appearance of a TCA-insoluble copper fraction in plasma. Levels of TCA-insoluble copper were highest in the first month of supplementation, afterwards levels declined. Caeruloplasmin activities were related to the levels of TCA-soluble Cu in plasma. In the Mo and S supplemented animals activities fell whereas in the control animals caeruloplasmin was unaffected. There was some correlation between the copper in the TCA-soluble plasma fraction and total liver copper ( r = 0·7928) and a better correlation ( r = 0·8448) between the TCA-insoluble plasma fraction and the copper of the nuclear fraction in liver. Regression equations were derived from the data which relate the total copper in liver and in the nuclear fraction to copper levels in these plasma fractions.

Studies of the changes in systemic copper metabolism and excretion produced by the intravenous administration of trithiomolybdate in sheep

1. The effects of intravenous trithiomolybdate administration on the fate of 64Cu and on stable Cu metabolism were examined in sheep held in metabolism cages and fed on a low-Cu diet supplying 2.95 mg Cu/animal per d. 2. In Expt 1 the injection of trithiomolybdate, 30 mg molybdenum/sheep per d for 5 d, greatly increased plasma Cu levels and more than doubled the faecal Cu excretion. Urinary Cu excretion was unaffected. The disappearance from plasma of 64Cu injected during the trithiomolybdate administration was slowed although faecal 64Cu excretion was increased more than threefold. 3. In Expt 2 trithiomolybdate, 10 and 30 mg Mo/sheep per d for 3 d, was administered 22 h after the injection of 64Cu. Radioactivity reappeared immediately in plasma and faecal 64Cu excretion was increased. 4. In both experiments the 64Cu and the increased stable Cu in plasma were associated with albumin. 5. The experiments explain the effectiveness of thiomolybdates as 'decoppering' agents and provide a model for some of the systemic effects seen in ruminants exposed to increased dietary Mo. The experiments support the view that the thiomolybdates, by causing the appearance of new ligands, alter the distribution of Cu in tissues and cause an overall depletion.

Studies on lambs from lines genetically selected for low and high copper status 2. Incidence of hypocuprosis on improved hill pasture

ABSTRACTGrowth rate and the concentrations of various biochemical constituents were measured in 2 years in lambs from two lines, selected on low (L) and high (H) copper (Cu) concentrations in plasma, and from two unselected pure breeds, Scottish Blackface (B) and Welsh Mountain (W). The lambs grazed improved hill pastures and half were given Cu supplements.H lambs were always heavier and were fattened for slaughter earlier than were L lambs, differences that were not completely eliminated when supplementary Cu was given. In both years, the improvements in growth rate due to supplementary Cu varied with genetic type (average L 20·5 (s.e. 2·5); H 5·7 (s.e. 2·6); B 25·1 (s.e. 3·7); W 8·1 (s.e. 3·3) g/day). Growth rates of supplemented lambs were L 100 (s.e. 2), H 104 (s.e. 2), B 134 (s.e. 5), W 103 (s.e. 3) g/day.At 6 weeks of age, unsupplemented lambs trom all genetic types were hypocupraemic and, at all ages, unsupplemented L and B lambs had lower concentrations of Cu in plasma and superoxide dismutase (SOD) activity than had unsupplemented H and W lambs. Supplemented lambs always had greater concentrations of Cu in plasma and SOD activities than had their unsupplemented counterparts. Supplementation increased the haemoglobin concentration for B (in year 2) and L lambs but not for H and W lambs. Cholesterol concentrations in plasma were unaffected by selection but were slightly higher in unsupplemented lambs. The concentration of total protein and the activity of aspartate transaminase were unaffected by genotype or Cu supplementation. In the liver of lambs at slaughter, the concentration of Cu was lower for unsupplemented lambs and inversely related to the concentration of iron.It was concluded that (i) genotype was an important determinant of hypocuprosis; (ii) the degree of hypocuprosis could not be predicted from herbage analyses alone, but instead may be predicted from biochemical assessment of the lamb; and (iii) the dose of Cu supplement used was inadequate for L and B lambs and recommended levels could be increased, within limits, without risk of toxicity.

Involvement of organic molybdenum compounds in the interaction between copper, molybdenum, and sulfur

The effect on Cu metabolism of two organic Mo compounds, cysteine-Mo (CM) and cysteine-Mo-S (CMS), and of an inorganic compound, tetrathiomolybate (TTM), was investigated in sheep. Intravenous administration of CMS or TTM increased total plasma Cu concentrations and promoted the appearance of trichloroacetic acid (TCA)-insoluble Cu in plasma. Plasma Mo was increased by both compounds. Column chromatography of plasma showed that CMS caused the accumulation of TCA-insoluble Cu in high-MW fractions, whereas TTM increased the Cu content oflow-MW fractions, mainly albumin. CMS and TTM increased the concentration of Cu and Mo in kidney. In liver, Mo concentrations were elevated by both CMS and TTM, and Cu concentrations were reduced by TTM when it was given at a low dose rate. The subcellular distribution of Cu and Mo in liver and kidney was investigated. The findings are discussed in relation to the proposal that Mo-containing, organic compounds are intermediaries in the interaction between Cu, Mo, and S in ruminants.

Retention of copper in the liver of sheep genetically selected for high and low concentrations of copper in plasma

ABSTRACTThe extent to which genetic selection to change the concentration of copper (Cu) in plasma also affected the retention of Cu in the liver was assessed in three experiments. In each, the concentration of Cu was measured in samples of liver (taken by biopsy) and of plasma from female sheep of lines selected from a Scottish Blackface × Welsh Mountain population (which had previously been interbred for several generations) for high and low plasma Cu levels (high line and low line) and from purebred Scottish Blackface and Welsh Mountain females.The concentration of Cu in the liver and plasma was found to be consistently greater in high-line and Welsh Mountain than in low-line and Scottish Blackface females (P < 0·01) in the first experiment in which grazing animals were sampled at both 6 and 10 months of age and in the second, where sampling' was at 6 months only. Mean Cu concentrations in the liver ranged from 13 to 115 mg/kg dry matter (DM) and the correlations with those in plasma varied from 0·28 to 0·53 (all P < 0·05) and was highest when the concentration of Cu in the liver was lowest. The correlation between the concentrations of Cu in liver at different ages was 0·57 (P < 0·05).In the third experiment, 10-month-old high- and low-line females were given complete diets containing either 5, 10, 22 or 28 mg Cu per kg DM for 12 weeks. Liver samples were obtained at the beginning and end of this period and blood samples were taken every 3 weeks. The concentration of Cu in the liver was greater in high- than in low-line sheep on all diets and increased linearly with the Cu concentration of the diet but at a greater rate in the high line. At the end, the high line had significantly greater concentrations of Cu in plasma on the 5 and 10 mg Cu per kg DM diets.The experiments showed that high-line females retained more Cu in the liver than low-line females. It is most likely that this was caused by a positive genetic correlation between concentration of Cu in plasma and the efficiency of absorption of Cu.

Genetic selection to produce lines of sheep differing in plasma copper concentrations

ABSTRACTMale lambs were selected annually at 18 and 24 weeks of age for high or low concentrations of copper in plasma to produce two closed lines. The difference between the high and low lines increased to approx. 0·5 mg/1 after 5 years when the experiment ended, indicating appreciable additive genetic variation for the concentration of Cu in plasma. The selection lines were derived from a population of Scottish Blackface × Welsh Mountain crosses which had been interbred for many generations. The two parental breeds contributing to the cross normally differ in a number of aspects of Cu status with that of the Welsh higher than that of the Blackface. Both pure breeds were kept as controls. In the final year, Cu concentrations of the high selection line exceeded the values of the Welsh and the low selection line had values below those of the Blackface. Differences between the selection lines persisted at all ages.There were indications of changes in the frequency of the Hb alleles, associated with the selection for Cu concentrations, but there were no correlated changes in body weight, reproductive performance or lamb mortality during the 5-year selection period when dietary supplies of Cu were not particularly restrictive.

The rôle of the breed of dam and of the breed of lamb in determining the copper status of the lamb. 2. Under a dietary regime moderately high in copper

ABSTRACTThe relative importance of the breed of dam and the breed of lamb in determining the copper status of the lamb was investigated by transferring embryos reciprocally between Scottish Blackface and Welsh Mountain ewes. A diet moderately high in Cu (8 mg/kg dry matter (DM)) was fed both to the ewes from mating onward and subsequently to their lambs.At birth, 9 and 24 weeks of age the concentration of Cu in the liver of lambs was the same for the two maternal breeds but within breed groups there was correspondence between full sibs when they were born to the same dam.By 9 weeks and at 24 weeks of age Welsh lambs, irrespective of their dam's breed, had greater concentrations of Cu in liver than Blackface lambs. The average concentration at 9 weeks was 190 and 130 mg/kg DM respectively for the two breeds of lamb.Results are also given for concentrations of Cu in plasma, kidney, brain, milk and faeces.The results differ from those found in the previous paper under a regime of low dietary Cu where the maternal breed affected concentration of Cu in the liver of lambs up to 9 weeks of age.

Effects of dietary supplements of thiomolybdates on copper and molybdenum metabolism in sheep

When 4 groups of 3 lambs were reared on a milk substitute containing 10·5 mg of Cu per kg DM with or without supplements of Cu, 5 mg, and Mo, 3 mg per kg DM in a 2×2 factorial design, Mo, given as ammonium tetrathiomolybdate (MoS 4) reduced hepatic Cu retention by one-third but had no effect on the amount or distribution of Cu in plasma or on plasma Mo concentrations. When 2 groups of 5 lambs were weaned on to a cereal-based diet containing 3·5 mg Cu per kg DM and one was given MoS 4 in the amount used previously, concentrations of Mo and TCA-insoluble Cu in plasma and the rate of depletion of liver Cu were increased. When Cu, 12 mg per kg DM, was finally added to both diets the plasma changes were reversed but the hepatic retention of Cu was still reduced. In a second experiment, 6 groups of 5 hypocupraemic ewes were repleted with a dietary Cu supplement in the presence of one of 3 Mo sources, molybdate (MoO 4), dithiomolybdate (MoO 2S 2) or tetrathiomolybdate (MoS 4) providing 3·0 mg Mo per kg DM each in the presence of low or high dietary S. The effects of the S supplement were dominant, causing the MoO 4 and MoO 2S 2 to behave like MoS 4 in impairing Cu and Mo absorption and inducing TCA-insoluble Mo and Cu to accumulate in the plasma: S enhanced these responses to MoS 4 even further. On the low S diet, the responses to MoO 4 and MoO 2S 2 were similar but small. It is concluded that at high dietary Mo and S concentrations, sufficient MoS 4 forms in the rumen and enters complexes with Cu to impair Cu absorption but that the formation of MoO 2S 2 does not play an important role in the Cu and Mo antagonism.

The effect of dietary molybdenum on hypocupraemic ewes treated by subcutaneous copper.

An attempt has been made to assess the importance of systemic sites of interaction from the effect of dietary molybdenum (Mo) on the protection afforded by a single sc injection of copper (Cu) to 29 initially hypocupraemic 5-year-old ewes, maintained on a low Cu diet. They were fed a diet of 1 kg/day containing 1.3 mg of Cu/kg supplemented with sodium sulphate which provided 1.7 gm of sodium per kg. Group A was given no further supplement. Group B was given added Mo, 25 mg/kg. Group C was given added Cu, 10 mg/kg. After 7 months, several animals in each group were injected sc with a single dose of 46.5 mg of Cu in the form of copper calcium edetate (Coprin). Blood samples were taken at intervals from the injected ewes over a 250-day period. All ewes were mated after 12 months on the diet. Injected ewes were approaching the 4th month of gestation when the last blood sample was taken at 250 days. Total Cu in plasma was determined by atomic absorption spectometry. Direct reacting Cu in plasma, cerulosplasmin oxidase activity, and hemoglobin were also estimated. Plasma Cu concentrations had increased to normal levels in 14 days in Group A after the Cu injections. Group B animals showed a greater increase, mean values exceeding those of Groups A and C, between Days 28-129 (p less than .01). Plasma Cu levels declined in ewes not given supplementary Cu after the 177th day. The final values for Groups A and B were similar to those found before injection. The direct reacting Cu in each group was increased after 7 days (p less than .05). This effect was most marked in the Mo supplemented ewes (Group B). The effect of Mo persisted until the final bleeding. Direct reacting Cu was only a minor part of the early response in total plasma copper of Group B ewes. Dietary Mo did not inhibit the incorporation of injected Cu into ceruloplasmin. The Mo-supplemented ewes were in poorer condition than copper-supplemented ewes. All groups gained in weight after the injections. The sc injection of Cu at 5 months prior to mating imporved fertility in Groups A and B. There was no evidence that dietary Mo impa ired the metabolism of parenteral Cu. However, it is known to deplete r uminants of Cu when the diet provides the only source of Cu. It is ther efore thought that the site of the Cu with Mo interaction is in the gut. If infertility due to Cu deficiency is suspected in a flock, an injection of Cu immediately prior to mating may improve conception rate and provide sufficient Cu to reduce the incidence of swayback.