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Metal (molybdenum, copper) accumulation and retention in brain, pituitary and other organs of ammonium tetrathiomolybdate-treated sheep

Published online by Cambridge University Press:  09 March 2007

Susan Haywood ,
Zuhal Dincer ,
J. Holding  and
Nicola M. Parry
Susan Haywood*
Affiliation:
Department of Veterinary Pathology, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK
Zuhal Dincer
Affiliation:
Department of Veterinary Pathology, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK
J. Holding
Affiliation:
Department of Clinical Chemistry, Duncan Building, Royal University Hospital, Prescot Street, Liverpool L69 3BX, UK
Nicola M. Parry
Affiliation:
Department of Veterinary Pathology, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK
*
*Corresponding author:Dr Susan Haywood, fax +44 (0) 151 794 4268.
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Abstract

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Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTM-treated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3·4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, testes and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0·02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0·02) and retained in the cerebellum and medulla oblongata in the TTM-treated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a strongly positive correlation (r 0·7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification.

Keywords

TetrathiomolybdateMolybdenumCopperToxicity
Type
Short Communication
Information
British Journal of Nutrition , Volume 79 , Issue 4 , April 1998 , pp. 329 - 331
Copyright
Copyright © The Nutrition Society 1998

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