Hostname: page-component-84b7d79bbc-g78kv Total loading time: 0 Render date: 2024-07-25T22:44:03.022Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  09 March 2007

S. R. Gooneratne ,
B. Laarveld ,
R. K. Chaplin  and
D. A. Christensen
S. R. Gooneratne
Affiliation:
Department of Animal and Poultry Science University of Saskatchewan, Saskatoon, Saskatchewan S7NOWO, Canada
B. Laarveld
Affiliation:
Department of Animal and Poultry Science University of Saskatchewan, Saskatoon, Saskatchewan S7NOWO, Canada
R. K. Chaplin
Affiliation:
Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7NOWO, Canada
D. A. Christensen
Affiliation:
Department of Animal and Poultry Science University of Saskatchewan, Saskatoon, Saskatchewan S7NOWO, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

1. The relative importance of excretory routes in the removal of recently stored 67Cu following tetrathiomolybdate (TTM) administration was studied. Lambs fed on either 5 mg Cu/kg dry matter (DM) or 35 mg Cu/kg DM, were primed intravenously (iv) with 67Cu and challenged 27 h later with 99Mo-labelled TTM given either iv or intraduodenally (id). The profiles of 67Cu and 99Mo and of Cu and Mo in blood, bile, urine and faeces were measured.

2. Level of dietary Cu and route of administration of 99Mo-TTM affected the amplitude of blood, bile and urine profiles of 67Cu and stable Cu, but not the pattern of the responses observed.

3. The present study describes for the first time increased excretion of endogenous 67Cu through gastrointestinal secretions other than bile due to TTM administration.

4. Administration of TTM resulted in the immediate release of 67Cu from storage compartments in the body into the blood circulation. Changes in stable Cu levels in blood, bile, urine and faeces, and gut and systemic effects were evident. Biliary and urinary Cu excretion due to TTM was rapid and maximal within 24 h of injection.

5. Administration of 67Cu iv resulted in the immediate excretion of 67Cu in bile in a pulsatile, constant pattern. A similar pattern of 67Cu excretion into bile in synchrony with that of 99Mo was observed after 99Mo-labelled TTM administration.

6. The similar pattern of biliary 67Cu excretion observed after injection of 67Cu and after injection of 99Mo-labelled TTM 27 h later is discussed in relation to the times required to process the Cu through different hepatic pathways for excretion in bile.

Type
Research Article
Information
British Journal of Nutrition , Volume 61 , Issue 2 , March 1989 , pp. 355 - 371
Copyright
Copyright © The Nutrition Society 1989

References

Banerjee, D., Onosaka, S. & Cherian, M. G. (1982) Immunohistochemical localization of metallothionein in cell nucleus and cytoplasm of rat liver. Toxicology 24, 95–105.CrossRefGoogle ScholarPubMed
Bremner, I. (1981). The nature and function of metallothionein. In Trace Element Metabolism in Man and Animals (TEMA-4), pp. 637–644 [Howell, J. McC., Gawthorne, J. M., White, C. L., editors]. Canberra: Australian Academy of Science.CrossRefGoogle Scholar
Caple, I. W. & Heath, T. J. (1972) Regulation of output of electrolytes in bile and pancreatic juice in sheep. Australian Journal of Biological Sciences 25, 155–165.Google Scholar
Charmley, L. L., Symonds, H. W. & Mallinson, G. B. (1982) The clearance of copper from the plasma of cattle and its excretion in bile during the intravenous infusion of copper sulphate solution. Proceedings of the Nutrition Society 41, 81A.Google Scholar
Chen, M. L. & Failla, M. L. (1988) Degradation of metallothionein (MT) in monolayer cultures of adult rat hepatocytes. Federation of American Societies for Experimental Biology Journal 2, A635.Google Scholar
Clarke, N. J. & Laurie, S. H. (1979) The copper–molybdenum antagonism in ruminants. I. The formation of thiomolybdates in animal rumen. Journal of Inorganic Biochemistry 12, 37–43.Google Scholar
Clarke, N. J., Laurie, S. H. & Pratt, D. E. (1987) The copper–molybdenum antagonism in ruminants. IV. Reaction of thiomolybdate ions with protein and metalloproteins. Inorganica Chimica Acta 138, 103–105.Google Scholar
De Duve, C. (1963). The lysosome concept. In Ciba Foundation Symposium on Lysosomes, pp. 1–31 [de Reuck, A. V. S., Cameron, M. P., editors]. Boston: Little, Brown & Co.Google Scholar
Dick, A. T., Dewey, D. W. & Gawthorne, J. M. (1975) Thiomolybdates and copper-molybdenum—sulphur interaction in ruminant nutrition. Journal of Agricultural Science, Cambridge 85, 567–568.Google Scholar
Farrer, P. A. & Mistilis, S. P. (1968). Copper metabolism in the rat. Studies of the biliary excretion and intestinal absorption of 64Cu labelled copper. Birth Defects 4, 14–22.Google Scholar
Gooneratne, S. R. (1986) Potential use of tetrathiomolybdate in copper storage diseases. Acta Pharmacologica et Toxicologica 59, Suppl. VII, 518–523.Google Scholar
Gooneratne, S. R., Chaplin, R. K., Trent, 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. & Christensen, D. A. (1984) Increased copper excretion in bile after thiomolybdate administration. Federation Proceedings 43, 790.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, 429–450.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, 469–480.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, 457–468.Google Scholar
Gooneratne, S. R., Laarveld, B., Chaplin, R. K. & Christensen, D. A. (1989a). 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. British Journal of Nutrition 61, 373–385.CrossRefGoogle Scholar
Gooneratne, S. R., Laarveld, B. & Christensen, D. A. (1987). Tetrathiomolybdate in the treatment of copper storage diseases. In Toxicology of Metals: Clinical and Experimental Research, pp. 321–322 [Brown, S. S., Kodama, Y., editors]. Chichester: Ellis Horwood.Google Scholar
Gooneratne, S. R., Laarveld, B. & Christensen, D. A. (1989b). Effect of 67Cu and 99Mo labelled tetrathiomolybdate on the distribution of 67Cu, Cu and 99Mo in bile fractions in sheep. Journal of Inorganic Biochemistry (In the Press.)Google Scholar
Humphries, W. R., Mills, C. F., Greig, A., Roberts, L., Inglis, D. & Halliday, G. J. (1986) Use of ammonium tetrathiomolybdate in the treatment of copper poisoning in sheep. Veterinary Record 119, 596–599.Google Scholar
Hynes, M., Lamand, M., Montel, G. & Mason, J. (1984). Some studies on the metabolism and the effects of99 Mo and 35S-labelled thiomolybdates after intravenous infusion in sheep. British Journal of Nutrition 52, 149–158.CrossRefGoogle Scholar
Jeunet, F., Richterich, R. & Aebi, H. (1962) Bile et céruloplasmine; étude in vitro à l'aide de la perfusion du foie de rat isolé. Journal of Physiology 54, 729–737.Google 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, 273–282.Google Scholar
Ke, Y. & Symonds, H. W. (1986) The effect of molybdate compounds on the biliary excretion of copper by sheep. Proceedings of the Nutrition Society 46, 69A.Google Scholar
Kelleher, C. A. & Ivan, M. (1985). Hepatic subcellular distribution of copper and 99Mo in sheep following intravenous administration of copper sulfate and [99Mo]-tetrathiomolybdate. In Trace Element Metabolism in Man and Animals (TEMA-5), pp. 364–367 [Mills, C. F., Bremner, I., Chesters, J. K., editors]. Slough: Commonwealth Agricultural Bureaux.Google Scholar
Kloppel, T. M., Brown, W. R. & Reichen, J. (1986) Mechanism of secretion of proteins into bile: studies in the perfused rat liver. Hepatology 6, 587–594.CrossRefGoogle ScholarPubMed
Kressner, M. S., Stockert, R. J., Morell, A. G. & Sternlieb, I. (1984) Origins of biliary copper. Hepatology 4, 867–870.CrossRefGoogle ScholarPubMed
Layden, T. J., Elias, E. & Boyer, J. L. (1978) Bile formation in the rat: the role of the paracellular shunt pathway. Journal of Clinical Investigation 62, 1375–1385.Google Scholar
Lewis, C. D. & Laemmli, U. K. (1982) High order metaphase chromosome structure: evidence for metalloprotein interactions. Cell 29, 171–174.CrossRefGoogle ScholarPubMed
Lewis, K. O. (1973) The nature of the copper complexes in bile and their relationship to the absorption and excretion of copper in normal subjects and in Wilson's disease. Gut 14, 221–232.CrossRefGoogle Scholar
Marcilese, N. A., Ammerman, C. G., Valsecchi, R. M., Dunavant, B. G. & Davis, G. K. (1970) Effect of dietary molybdenum and sulfate upon urinary excretion of copper in sheep. Journal of Nutrition 100, 1399–1405.Google Scholar
Mason, J., Kelleher, C. A. & Letters, J. (1982a). The demonstration of protein-bound 99Mo-di- and trithiomolybdate in sheep plasma after the infusion of 99Mo-labelled molybdate into the rumen. British Journal of Nutrition 48, 391–397.CrossRefGoogle Scholar
Mason, J., Lamand, M. & Kelleher, C. (1980). The fate of 99Mo-labelled sodium tetrathiomolybdate after duodenal administration in sheep: the effect of caeruloplasmin (EC 1. 16.3.1) diamine oxidase activity and plasma copper. British Journal of Nutrition 43, 515–523.Google ScholarPubMed
Mason, J., Lamand, M. & Kelleher, C. A. (1982b). The effects of duodenal infusion of tri- and dithiomolybdate on plasma copper and on the diamine oxidase activity of caeruloplasmin (EC 1.16.3.1) in sheep. Journal of Comparative Pathology 92, 509–518.Google Scholar
Mason, J., Lamand, M., Tressel, J. C. & Mulryan, G. (1988) Studies of the changes in systemic copper metabolism and excretion produced by the intravenous administration of trithiomolybdate in sheep. British Journal of Nutrition 59, 289–300.Google Scholar
Mehra, R. K. & Bremner, I. (1985) Studies on the metabolism of rat liver copper metallothionein. Biochemical Journal 227, 903–908.Google Scholar
Mills, C. F. (1985). Changing perspectives in studies of the trace elements and animal health. In Trace Element Metabolism in Man and Animals (TEMA-5), pp. 1–10 [Mills, C. F., Bremner, I., Chesters, J. K., editors]. Slough: Commonwealth Agricultural Bureaux.Google Scholar
Mistilis, S. P. & Farrer, P. A. (1968) The absorption of biliary and non-biliary radiocopper in the rat. Scandinavian Journal of Gastroenterology 3, 586–592.Google Scholar
Mullock, B. M., Dobrota, M. & Hinton, R. H. (1978) Sources of proteins of rat bile. Biochimica et Biophysica Acta 543, 497–507.CrossRefGoogle Scholar
Phillippo, M. & Graca, D. S. (1983) Biliary copper secretion in cattle. Proceedings of the Nutrition Society 42, 46A.Google Scholar
Price, J., Will, A. M., Paschaleris, G. & Chesters, J. K. (1987). Identification of thiomolybdates in digesta and plasma from sheep after administration of 99Mo-labelled compounds into the rumen. British Journal of Nutrition 58, 127–138.CrossRefGoogle Scholar
Samuels, A. R., Freedman, J. H. & Bhargava, M. M. (1983) Purification and characterization of a novel abundant protein in rat bile that binds azo dye metabolites and copper. Biochimica et Biophysica Acta 759, 23–31.Google Scholar
Sato, M. & Bremner, I. (1984) Biliary excretion of metallothionein and a possible degradation product in rats injected with copper and zinc. Biochemical Journal 223, 475–479.Google Scholar
Smith, B. S. W. & Wright, H. (1975) Copper molybdenum interaction. Effect of dietary molybdenum on the binding of copper to plasma proteins in sheep. Journal of Comparative Pathology 85, 299–305.Google Scholar
Sternlieb, I. & Quintana, N. (1985) Biliary proteins and ductular ultrastructure. Hepatology 5, 139–143.CrossRefGoogle ScholarPubMed
Suttle, N. F. & Field, A. C. (1983) Effects of dietary supplements of thiomolybdates on copper and molybdenum metabolism in sheep. Journal of Comparative Pathology 93, 379–389.Google Scholar
Terao, T. & Owen, C. A. Jr (1973) Nature of copper compounds in liver supernate and bile of rats: studies with Cu. American Journal of Physiology 224, 682–686.Google Scholar
Van den berg, G. J. & Van den Hamer, C. J. A. (1984) Trace metal uptake in liver cells. 1. Influence of albumin in the medium on the uptake of copper by hepatoma cells. Journal of Inorganic Biochemistry 22, 73–84.Google Scholar
Walshe, J. M. (1986). Tetrathiomolybdate (MoS4) as an ‘anticopper’ agent in man. In Orphan Diseases/Orphan Drugs, pp. 76–85 [Scheinberg, I. H., Walshe, J. M., editors]. Manchester: Manchester University Press.Google Scholar
Wang, Z. Y., Poole, D. B. R. & Mason, J. (1987). The uptake and intracellular distribution of [35S]-trithiomolybdate in bovine liver in vivo. Journal of Inorganic Biochemistry 31, 85–93.CrossRefGoogle 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, 261–273.Google Scholar