Molybdenum toxicity: Interactions between copper,molybdenum and sulphate

Molybdenum toxicity and the interactions between copper, molybdenum and sulphate are reviewed. The main signs of molybdenum poisoning are poor growth and anaemia (rat, chick, rabbit, cattle and sheep), anorexia (rat), diarrhoea and achromotrichia (cattle and sheep), joint and bone deformities (rat, rabbit, cattle), central nervous system degeneration and loss of crimp in wool (sheep). The following topics are discussed:

1. The effect of sulphate and sulphur compounds on molybdenum toxicity.
2. The effect of molybdenum on tissue copper levels.
3. The effect of molybdenum on the distribution of copper in plasma.
4. The effect of molybden8m on uptake and excretion of copper.
5. The possible existence of copper(II) molybdate in vivo.
6. The influence of molybdenum on sulphide production by ruminal micro-organisms.
7. Competition between molybdenum and sulphate in intestinal transport.
8. Interaction of sulphur with copper in vivo.
9. The possible involvement of molybdenum in gout and multiple sclerosis in humans.

     

Relationships between swayback incidence and concentration of copper in the blood of sheep of different breeds

In 2 flocks of sheep each comprising several breeds which had suffered differing losses from swayback in 1964, a comparison of blood Cu levels of ewes born in the swayback year and others born in years when swayback had not occurred suggested that swayback had removed the lambs with lower than average Cu levels, and that the consequences of this persisted into adulthood. The unaffected survivors as a group had a correspondingly higher average level of Cu in their blood.     

Effect of copper sulphate on alpha-ketoglutarate metabolism in the digestive gland of the snail host, Lymnaealuteola

Significant drop in the size of fuel depots was noted in copper sulphate treated snails. Free amino acid levels dropped and lactate level increased. The effects of copper treatment on rates of fuel oxidation and ammonia production in the presence of exogenously added alpha-ketoglutarate were evaluated. 92% drop in Kg dh complex activity, 33% drop in Alanine amino transferase (ALAT) activity with 78% rise in Glucose-6-phosphatase activity were recorded. Results were discussed in relation to metal ion binding with proteins and its inhibitory effect on alpha Kg dh complex enzyme activity. Molluscicidal activity of copper was found to be due to metabolic block in the TCA cycle at the alpha-ketoglutarate level.     

Effect of dietary D-penicillamine on metabolism of copper in the rat.

When normal rats were put on a diet containing d-penicillamine equivalent to a dosage of about 1.75 g/day in a 70-kg man, there was a prompt, marked decrease in biliary excretion of copper and of radiocopper after its intravenous administration. Urinary copper increased as tissue copper levels decreased; this decrease was most pronounced in bone marrow, kidney, lung, and spleen. Plasma copper increased and p-phenylendiamine oxidase activity increased. Fecal copper decreased modestly, which was probably attributable to decreases in food intake and biliary copper. Copper-toxic rats, already hypercupriuric, excreted more urinary copper when given d-penicillamine.     

Effect of glucagon on plasma alanine and glutamine metabolism and hepatic gluconeogenesis in sheep.

Net hepatic uptakes of plasma alanine (Ala), glutamate (Glu), and glutamine (Gln) were measured before and during intraportal glucagon infusions in five normaland four insulin-and alloxan-treated (ITA), conscious, fed sheep. Since hyperinsulinemia is associated with glucagon administration, ITA sheep were used so that constant plasma insulin levels could be maintained. Glucose turnover was determined by a vena caval infusion of glucose-6-'3H. In addition, in ITA sheep, Ala-'14C wasinfused for measurement of plasma Ala turnover, its unidirectional organ metabolism, and contribution to glucose synthesis. During infusion of glucagon, the net hepatic uptake of Ala increased significantly (P is less than 0.01) from control values of 3.8 plus or minus 0.5 and 2.7 plus or minus 0.6 mmol/h to 5.9 plus or minus 1.0 and 5.5 plus or minus 0.8 mmol/h in normal and ITA sheep, respectively. Similarly, Gin uptake increased from 4.3 plus or minus 1.4 and 1.6 plus or minus 0.5 to 5.5 plus or minus1.6 and 3.7 plus or minus 1.0 mmol/h, respectively. The conversion of Ala to glucose increased from control values of 1.7 plus or minus 0.5 to 3.0 plus or minus 0.5 mmol/h.Arterial plasma Ala and Gin concentrations decreased about 25% during glucagon administration, presumably as a result of their increased hepatic uptakes. A decreasein utilization of plasma Ala, but no change in production was calculated for the nonhepatic tissues, indicating that glucagon increased gluconeogenesis from Ala at the expense of muscle protein synthesis. Glucagon thus has a direct effect on the liver butonly an indirect effect on other tissues.     

Effect of training on maximum oxygen intake and on anaerobic metabolism in man

Summary The concentration of lactate and pyruvate was determined in the blood of 13 subjects at three aerobic and four anaerobic levels of work before and after a period of training on a constant work-rate bicycle ergometer. In addition each man's maximum oxygen intake was established on either the bicycle ergometer or the motor-driven treadmill, by means of the Douglas bag technique, before and after the period of training.The results obtained demonstrated that a regime of training influenced the maximum oxygen intake and also the level of oxygen intake at which excess lactate starts to appear in the blood. During the training of the subjects these two physiological parameters changed independently of each other but large individual differences were also observed. The mean maximum oxygen intake of the men, which was 2.888l/min before training, increased to 3.060l/min (a change of 7 per cent) after the men had trained for a period of 4 to 16 weeks. During this period of training the mean level of oxygen intake, expressed as a percentage of the maximum value, at which excess lactate appeared increased from 46 to 62 per cent.The relationship between the degree of fitness and the appearance of anaerobic metabolism during work is discussed. In untrained individuals the onset of anaerobic metabolism occurred at 40–45 per cent of the maximum oxygen intake, in trained individuals at 55–60 per cent and in the exceptionally well-trained men at about 70 per cent.     

Effect of intravenously administered tetrathiomolybdate on plasma copper concentrations of copper-loaded sheep

Chronic copper toxicity was induced in 14 ewes in two groups by oral dosing with CuSO4. Copper dosing was stopped in sheep of groups 1 and 2 at the first rise of serum acid phosphatase activity and on the first day of haemolysis, respectively. Thiomolybdate was administered intravenously (i.v.) to sheep of group 2 at the rate of 100 mg on the first day of haemolysis and at 24-h intervals, with a maximum of 3 doses during haemolysis. Thiomolybdate was also given intravenously at a dose of 50 mg twice weekly for 11 weeks to four sheep of group 1 after the cessation of copper dosing (group 1B) and to five sheep of group 2 at the end of haemolysis. Plasma copper concentration was determined before and 24 h after each injection of 50 mg thiomolybdate and "elevations" of plasma copper concentration were seen after each injection of thiomolybdate. The differences between plasma copper concentrations observed before and after each thiomolybdate injection for doses 1 to 11 were significantly higher than those seen for doses 12 to 22. Following thiomolybdate administration, the copper content of the liver of sheep in groups 1B and 2 was reduced much more than in sheep of group 1A, in which copper dosing also ceased but which did not receive thiomolybdate. It was concluded that the high plasma copper response to thiomolybdate doses 1 to 11 was due to an influx of copper into the bloodstream from the heavily copper-loaded liver cells. The lower plasma copper response during the latter part of thiomolybdate administration was due to a gradual reduction in the amount of copper entering the bloodstream from the liver cells, as these cells became depleted of copper. Some of this copper may become part of the glomerular filtrate and be taken up by the cells of the proximal convoluted tubules of the kidney or may be excreted in the urine.     

Effect of acute maternal starvation on tyrosine metabolism and protein synthesis in fetal sheep

To determine the effects of acute maternal starvation on intrauterine growth, tyrosine concentration and specific activity values in plasma, intracellular free and protein bound pools were determined in catheterized ovine fetuses following an 8 h continuous infusion of L-[2,3,5,6 3H] or L-[U-14C] tyrosine into the ewe and fetus respectively at 115-125 days of gestation. From the kinetic data the rates of whole body and tissue fractional protein synthesis were calculated. Although placental protein synthesis was not significantly changed as a result of acute maternal starvation, fetal whole body protein synthesis was reduced from 63 g/d/kg in the fed to 25 g/d/kg in the starved condition. There was also a 10 fold reduction in the net placental transfer of tyrosine to the fetus in the starved ewes. In addition, a three fold increase was observed in the quantity of tyrosine used for oxidation by the fetuses of starved ewes, changing from 5.2% of tyrosine net utilization in the fed to 13.7% in the starved condition. Significant reductions in tissue fractional protein synthesis rates were also seen in the liver, brain, lung kidney and GIT tissues from 78, 37, 65, 45 and 71%/d respectively in the fed to 12, 10, 23, 22 and 35%/d in the fetuses of starved ewes. The data indicate that during acute maternal starvation the sheep fetus utilizes more tyrosine for oxidation and less for anabolic purposes which is reflected in a decrease both in whole body and tissue fractional rates of protein synthesis.     

Glutamine metabolism, interorgan transport and glucogenicity in the sheep

[U-14C]glutamine and [6-3H]glucose were infused into four groups of sheep: fed, NH4Cl acidotic, fasted, and dexamethasone treated. Net and unidirectional plasma glutamine fluxes in the portal-drained viscera (PDV), liver, kidneys, and hindquarters were measured by multiplying venoarterial concentration differences and 14C extraction ratios by the rate of blood flow. In fed sheep, glutamine was released by kidneys and muscle but removed by PDV and liver. In all other sheep, renal glutamine release either decreased or switched over to net removal largely due to increased unidirectional renal utilization. This increased renal glutamine demand was compensated for, during acidosis, by a decreased net hepatic glutamine removal but, during fasting and dexamethasone treatment, by an increased muscle glutamine release. Plasma glutamine and glucose turnover rates averaged 11-12 and 19-24 mmol/h but the percentage of glutamine converted to glucose was higher during fasting and dexamethasone treatment (21%) than in normal fed sheep (17%) perhaps reflecting the increased glutamine removal by the kidneys. Since renal glutamine utilization increases with acidosis and fasting and, since glutamine turnover remains unchanged, glutamine metabolism by other body tissues must be altered to compensate for renal changes.     

Comparing serum and hepatic concentrations of iron, copper, and cobalt in healthy sheep and sheep with chronic fasciolosis

Fasciolosis is one of the most important parasitic diseases of ruminants. This parasite causes liver dysfunction which may contribute to albumin synthesis and copper transferring to the liver and also reduces the elemental storage. Due to these reasons and to determine the effects of fasciolosis on serum and liver iron, copper, and cobalt status, the present study was conducted on 460 slaughtered sheep. During antemortem examination and after giving an identification number, blood samples were taken, and age, sex, and origin of animals were recorded. Visual inspection and palpation were performed on the liver to determine Fasciola infestation; then, liver samples were taken from 100 sheep (50 infested and 50 healthy ones), and the concentration of the mentioned minerals was measured by atomic absorption spectrophotometry. The results indicated that liver iron, copper, and cobalt concentrations in healthy sheep (74.47, 32.95, and 0.13 ppm, respectively) were significantly higher than those in sheep with fasciolosis (36.78, 11.22, and 0.05 ppm, respectively) (P?<?0.05). These findings may explain the role of hepatic injuries caused by fasciolosis on mineral status and also the role of minerals on parasite persistency.