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Profiles of 67Cu in blood, bile, urine and faeces from 67Cu-primed lambs: effect of 99Mo-labelled tetrathiomolybdate on the metabolism of 67Cu after long-term storage

Published online by Cambridge University Press:  09 March 2007

S. R. Gooneratne
Affiliation:
Department of Animal and Poultry Science and University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO, Canada
B. Laarveld
Affiliation:
Department of Animal and Poultry Science and University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO, Canada
R. K. Chaplin
Affiliation:
Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO, Canada
D. A. Christensen
Affiliation:
Department of Animal and Poultry Science and University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO, Canada
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Abstract

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1. The effectiveness of tetrathiomolybdate (TTM) in the removal of 67Cu from the long-term storage compartment in liver was studied. Lambs receiving 5 mg Cu/kg dry matter (DM) or 35 mg Cu/kg DM were primed intravenously (iv) with 67Cu and challenged 10 d later with 99Mo-labelled TTM given either iv or intraduodenally (id). The profiles of 67Cu and 99Mo and of Cu and Mo with time were measured in blood, bile, urine and faeces.

2. The level of dietary Cu affected the amplitude of profiles of 67Cu and Cu in blood, bile and urine after administration of 99Mo-labelled TTM. TTM administration increased liver Cu removal and this was most marked in sheep given TTM iv. The liver Cu removal from the long-term storage Cu compartment was low and was not affected by the route of administration of TTM. Endogenous Cu excretion was higher in lambs given TTM id.

3. Excretion of 67Cu in bile through the transhepatocellular pathway after TTM administration appeared absent, while the transbiliary and hepatolysosomal pathways were operative. The potential reasons for this change are discussed.

4. TTM predominantly enhances the removal of Cu from the short-term storage compartment, but effects on the long-term storage compartment may still be of significance.

Type
Research Article
Copyright
Copyright © The Nutrition Society 1989

References

Barka, T., Scheuer, P. J., Schaffner, F. & Popper, H. (1964) Structural changes of liver cells in copper intoxication. Archives of Pathology 78, 331349.Google Scholar
Dick, A. T., Dewey, D. W. & Gawthorne, J. M. (1975) Thiomolybdates and the copper-molybdenum-sulphur interaction in ruminant nutrition. Journal of Agricultural Science, Cambridge 85, 567580.Google Scholar
Fell, B. F., Dinsdale, D. & El-Gallad, T. T. (1979) Gut pathology of rats dosed with tetrathiomolybdate. Journal of Comparative Pathology 89, 495514.Google Scholar
Goldfischer, S. & Sternlieb, I. (1968) Changes in the distribution of hepatic copper in relation to the progression of Wilson's disease (hepatolenticular degeneration). American Journal of Pathology 53, 883901.Google Scholar
Gooneratne, S. R. (1986) Potential use of tetrathiomolybdate in copper storage diseases. Acta Pharmacologica et Toxicologica 59, Suppl. VII, 518523.Google Scholar
Gooneratne, S. R., Chaplin, R. K., TrentA. M., A. M., & Christensen, D. A. (1988). Effect of tetrathiomolybdate administration on the excretion of copper, zinc, iron and molybdenum in sheep bile.British Veterinary Journal (In the Press.)Google Scholar
Gooneratne, S. R., Howell, J. McC. & Cook, R. D. (1980) An ultrastructural and morphometric study of the liver of normal and copper-poisoned sheep. American Journal of Pathology 99, 429450.Google Scholar
Gooneratne, S. R., Howell, J. McC. & Gawthorne, J. M. (1979) Intracellular distribution of copper in the liver of normal and copper loaded sheep. Research in Veterinary Science 16, 5764.Google Scholar
Gooneratne, S. R., Howell, J. McC. & Gawthorne, J. M. (1981a) An investigation of the effects of thiomolybdate on copper metabolism in chronic Cu-poisoned sheep. British Journal of Nutrition 46, 469480.Google Scholar
Gooneratne, S. R., Howell, J. McC. & Gawthorne, J. M. (1981b) Intravenous administration of thiomolybdate for the treatment and prevention of chronic copper poisoning in sheep. British Journal of Nutrition 46, 457468.Google Scholar
Gooneratne, S. R., Laarveld, B., Chaplin, R. K. & Christensen, D. A. (1989). Profiles of 67Cu in blood, bile, urine and faeces from 67Cu-primed lambs: effect of 99Mo-labelled tetrathiomolybdate on the metabolism of recently stored tissue 67Cu. British Journal of Nutrition 61, 355371.Google Scholar
Hynes, M., Lamand, M., Montel, G. & Mason, J. (1984). Some studies on the metabolism and the effects of 99Mo-and 35S-labelled thiomolybdates after intravenous infusion in sheep. Journal of Inorganic Biochemistry 24, 279288.CrossRefGoogle Scholar
Jones, H. B., Gooneratne, S. R. & Howell, J. McC. (1984) X-ray microanalysis of liver and kidney in copper loaded sheep with and without thiomolybdate administration. Research in Veterinary Science 37, 273279.Google Scholar
Lindquist, R. R. (1968) Studies on the pathogenesis of hepatolenticular degeneration. III. The effect of copper on rat liver lysosomes. American Journal of Pathology 53, 903927.Google Scholar
Mason, J. (1986) Thiomolybdates: mediators of molybdenum toxicity and enzyme inhibitors. Toxicology 42, 99109.CrossRefGoogle ScholarPubMed
Mills, C. F., Bremner, I., El-Gallad, T. T., Dalgarno, A. C. & Young, B. W. (1978). Mechanisms of molybdenum/sulphur antagonism of copper utilization by ruminants. In Trace Element Metabolism in Man and Animals (TEMA-3), pp. 150158 [Kirchgessner, M., editor]. Weihenstephan: Arbeitskreis für Tierernäh-rungsforschung.Google Scholar
Read, R., Sutherland, J. & Ghosh, P. (1986) The matrix components of the epiphyseal growth plate and articular cartilage from dogs treated with ammonium tetrathiomolybdate, a copper antagonist. Australian Journal of Experimental Biology and Medical Science 64, 545562.Google Scholar
Sternlieb, I. (1972). Evolution of the hepatic lesion in Wilson's disease (hepatolenticular degeneration). In Progress in Liver Diseases, vol IV, pp. 511525. [Popper, H. and Schaffner, F., editors]. New York, London: Grune and Stratton.Google Scholar
Sternlieb, I. (1980) Copper and the liver. Gastroenterology 78, 16151628.Google Scholar
Suttle, N. F. (1980) The role of thiomolybdate in the nutritional interactions of copper, molybdenum and sulfur: fact or fantasy? Annals of the New York Academy of Science 355, 195204.Google ScholarPubMed
Underwood, E. J. (1977) Trace Elements in Human and Animal Nutrition, 4th ed. New York and London: Academic Press.Google Scholar
Walshe, J. M. (1984) Copper: its role in the pathogenesis of liver disease. Seminars in Liver Disease 4, 252263.Google Scholar
Walshe, J. M. (1986). Tetrathiomolybdate (MoS4) as an ‘anticopper’ agent in man. In Orphan Diseases/Orphan Drugs, pp. 7685 [Scheinberg, I. H., Walshe, J. M., editors]. Manchester: Manchester University Press.Google Scholar
Weber, K. M., Boston, R. C. & Leaver, D. D. (1980) A kinetic model for copper metabolism in sheep. Australian Journal of Agricultural Research 31, 773790.Google Scholar
Weber, K. M., Boston, R. C. & Leaver, D. D. (1983) The effect of molybdenum and sulphur on the kinetics of copper metabolism in sheep. Australian Journal of Agricultural Research 34, 295306.Google Scholar
Woods, M. & Mason, J. (1987) Spectral and kinetic studies on the binding of trithiomolybdate to bovine and canine serum albumin in vitro: the interaction with copper. Journal of Inorganic Biochemistry 30, 261273.Google Scholar