Effects of D-penicillamine on urinary copper excretion in high-copper supplemented sheep.

The effects of a single oral application of D-penicillamine (DPA, mean dosage 28 mg/kg body weight) on urinary copper (Cu) excretion and general renal function in six high-Cu supplemented sheep (Cu intake of 3.7 mg/day per kg body weight for 84 days) and four controls (Cu intake of 0.16 mg/day per kg body weight) were investigated to quantify induced cupruresis and the therapeutic effect of DPA as a decoppering agent. Changes in liver Cu concentration were examined before and after DPA treatment by liver biopsies. The influence of DPA treatment on general renal function was low. A 10-fold increase in renal Cu excretion was induced in both groups of sheep. Maximal Cu excretion was observed 4 h after DPA treatment, with mean values of 280 pmol/min per kg body weight in the high Cu group and 145 pmol/min per kg body weight in the controls. In the high Cu sheep, urinary Cu excretion within 24 h after DPA application was equivalent to only 0.42 +/- 0.26% of liver Cu content (mean concentration 347 +/- 124 mg/kg wet weight). Moreover, no effect of DPA on liver Cu concentration was evident. These findings demonstrate that a single application of DPA is not effective in inducing sufficient Cu loss from the bodies of Cu-loaded sheep.

[1]  M. Ganter,et al.  Long-term observation of subclinical chronic copper poisoning in two sheep breeds. , 2001, Journal of veterinary medicine. A, Physiology, pathology, clinical medicine.

[2]  M. Murphy,et al.  Diagnosis and treatment of copper toxicosis in ruminants. , 1999, Journal of the American Veterinary Medical Association.

[3]  M. Coenen,et al.  [Photometric determination of copper content in the liver during experimental chronic copper poisoning in sheep]. , 1997, DTW. Deutsche tierarztliche Wochenschrift.

[4]  S. Gooneratne,et al.  Effect of chelating agents on the excretion of copper, zinc and iron in the bile and urine of sheep. , 1997, Veterinary journal.

[5]  K. Bickhardt,et al.  [Clinical studies of kidney function in sheep. I. Methods and reference values of healthy animals]. , 1994, DTW. Deutsche tierarztliche Wochenschrift.

[6]  M. C. Williams,et al.  The cupruretic effect of two chelators following copper loading in sheep. , 1993, Veterinary and human toxicology.

[7]  J. Mason,et al.  The interactions of penicillamine with copper in vivo and the effect on hepatic metallothionein levels and copper/zinc distribution: the implications for Wilson's disease and arthritis therapy. , 1992, The Journal of laboratory and clinical medicine.

[8]  B. Portmann,et al.  Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson's disease , 1992, Hepatology.

[9]  H. J. West,et al.  Changes in the concentrations of bile acids in the plasma of sheep with liver damage. , 1987, Research in veterinary science.

[10]  M. Hidiroglou,et al.  Copper poisoning in a flock of sheep. Copper excretion patterns after treatment with molybdenum and sulfur or penicillamine. , 1984, The Canadian veterinary journal = La revue veterinaire canadienne.

[11]  P. Welling,et al.  Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate , 1983, Clinical pharmacology and therapeutics.

[12]  R. Boston,et al.  A kinetic model of copper metabolism in sheep. , 1980 .

[13]  J. Aaseth,et al.  The Mobilization of Copper in Sheep by Chelating Agents , 1978, Acta Veterinaria Scandinavica.

[14]  C. Gopinath,et al.  Experimental chronic copper toxicity in sheep. Biochemical and haematological studies during the development of lesions in the liver. , 1972, Research in Veterinary Science.