scholarly journals Evaluation of a commercially available molybdate formulation and zinc oxide boluses in preventing hepatic copper accumulation and thus enzootic icterus in sheep

Author(s):  
C.J. Botha ◽  
A.S. Shakespeare ◽  
R. Gehring ◽  
D. Van der Merwe

The efficacy of a molybdate formulation and a zinc oxide bolus as prophylactic agents for enzootic icterus was evaluated in sheep. Before copper loading, liver biopsies were performed on 12 male, 6-month-old, Mutton Merino sheep to determine hepatic copper (Cu) and zinc (Zn) concentrations. The animals were restrictively randomised according to liver copper concentrations to 3 treatment groups (n = 4) to achieve similar mean liver copper concentrations per group. All sheep received 4 m /kg of a 0.5 %aqueous solution of CuSO4·5H2O intraruminally 7 days per week for 10 weeks. On Day 0 the sheep in the Mo-group were injected subcutaneously with 42 mg molybdenum (Mo) contained in a commercial molybdate formulation. The animals in the Zn-group each received a zinc oxide bolus, containing 43 g zinc oxide, via a rumen cannula. Treatment was repeated on Day 42. Four animals served as untreated controls. Urinary copper excretion, plasma copper concentration, haematocrit and glutamate dehydrogenase (GLDH) activity were determined throughout the trial. The animals were sacrificed after 10 weeks and liver samples were submitted for histopathological examination. Liver and kidney copper and zinc concentrations were determined. Neither the molybdate treatment nor the zinc oxide boluses prevented hepatic copper accumulation. The urinary copper excretion, plasma copper concentration, haematocrit and GLDH activity were not significantly different (P > 0.05) from the controls.

2010 ◽  
Vol 42 ◽  
pp. S373
Author(s):  
G. Ranucci ◽  
E. Nicastro ◽  
C. Della Corte ◽  
M. Tufano ◽  
P. Vajro ◽  
...  

2020 ◽  
pp. 1098612X2096135
Author(s):  
Punyamanee Yamkate ◽  
Randi M Gold ◽  
Panagiotis G Xenoulis ◽  
Katja Steiger ◽  
David C Twedt ◽  
...  

Objectives The aim of this study was to assess hepatic copper concentrations and zonal distribution in cat liver specimens. Methods For this study, 121 archived, formalin-fixed, paraffin-embedded liver specimens from cats were used. Tissue sections were stained for copper with rhodanine and scored from 0 (no copper accumulation) to 5 (panlobular copper accumulation). The tissue specimens were then deparaffinized and hepatic copper concentrations were measured using flame atomic absorption spectroscopy. Results Tissue samples were categorized into four groups based on histopathologic findings: (1) no significant histopathologic hepatic changes (n = 66); (2) hepatic steatosis (n = 18); (3) inflammatory or infectious disease (n = 24); and (4) neoplasia (n = 13). Of the 121 specimens, 13 (11%) stained positive for copper, with three having a score ⩾3. Thirty-seven specimens (31%) had copper concentrations above the reference interval ([RI] <180 µg/g dry weight liver). Copper concentrations in cats with hepatic inflammatory or infectious disease were significantly higher than cats with hepatic steatosis ( P = 0.03). Copper-staining score and concentration were positively correlated ( rs = 0.46, P <0.001). Conclusions and relevance Despite the fact that 31% of specimens had copper concentrations above the RI, only 11% showed positive copper staining and only 2.5% had a score ⩾3. Our findings suggest that hepatic copper concentrations greater than the upper limit of the RI are relatively common in cats. Further studies to determine the factors that influence hepatic copper staining in cats and to establish contemporary RIs for hepatic copper in healthy cats are warranted.


2020 ◽  
Vol 14 (1) ◽  
pp. dmm045963
Author(s):  
Amika Singla ◽  
Qing Chen ◽  
Kohei Suzuki ◽  
Jie Song ◽  
Alina Fedoseienko ◽  
...  

ABSTRACTCopper is an essential transition metal for all eukaryotes. In mammals, intestinal copper absorption is mediated by the ATP7A copper transporter, whereas copper excretion occurs predominantly through the biliary route and is mediated by the paralog ATP7B. Both transporters have been shown to be recycled actively between the endosomal network and the plasma membrane by a molecular machinery known as the COMMD/CCDC22/CCDC93 or CCC complex. In fact, mutations in COMMD1 can lead to impaired biliary copper excretion and liver pathology in dogs and in mice with liver-specific Commd1 deficiency, recapitulating aspects of this phenotype. Nonetheless, the role of the CCC complex in intestinal copper absorption in vivo has not been studied, and the potential redundancy of various COMMD family members has not been tested. In this study, we examined copper homeostasis in enterocyte-specific and hepatocyte-specific COMMD gene-deficient mice. We found that, in contrast to effects in cell lines in culture, COMMD protein deficiency induced minimal changes in ATP7A in enterocytes and did not lead to altered copper levels under low- or high-copper diets, suggesting that regulation of ATP7A in enterocytes is not of physiological consequence. By contrast, deficiency of any of three COMMD genes (Commd1, Commd6 or Commd9) resulted in hepatic copper accumulation under high-copper diets. We found that each of these deficiencies caused destabilization of the entire CCC complex and suggest that this might explain their shared phenotype. Overall, we conclude that the CCC complex plays an important role in ATP7B endosomal recycling and function.


1981 ◽  
Vol 60 (2) ◽  
pp. 207-212 ◽  
Author(s):  
J. Scott ◽  
W. Jenkins ◽  
G. P. Smith ◽  
T. J. Peters

1. Analytical subcellular fractionation in combination with enzymic microanalysis has been used to investigate the hepatic organelle pathology of primary biliary cirrhosis. Activities of plasma membrane and lysosomal enzymes in hepatic needle biopsies were increased, but marker enzymes for other organelles were normal. 2. Seven patients were treated with a low dose of penicillamine, 250 mg daily, over a 3–6 month period. The initially raised serum alkaline phosphatase and IgM levels were significantly reduced. In four patients with markedly elevated hepatic copper there was a small decrease, but urinary copper excretion was unaltered. Hepatic organelle pathology was significantly improved. 3. No serious side-effects were noted and it is suggested that a controlled trial of low-dose D-penicillamine therapy is indicated in patients with primary biliary cirrhosis.


1968 ◽  
Vol 8 (35) ◽  
pp. 679 ◽  
Author(s):  
RJW Gartner ◽  
JG Young ◽  
PM Pepper

A 2 X 2 factorial design was used to investigate the effects of copper and cobalt therapy of Hereford steers grazing Lotononis-Pangola pastures on the wet heath areas of coastal south-eastern Queensland. Copper was given as a subcutaneous injection of copper glycinate and cobalt as an intra- ruminal cobalt oxide pellet. Liver samples were obtained at three-monthly intervals for 18 months. The liver copper concentration of untreated animals decreased to low levels (<10 p.p.m.). Copper therapy increased (P<0.01) and cobalt therapy decreased (P<0.01) liver copper levels. There were, however, no significant differences in bodyweight gains.


2010 ◽  
Vol 5 (2) ◽  
pp. 14-15
Author(s):  
J. Logue ◽  
A. Duncan ◽  
C. Roxburgh ◽  
P. Horgan ◽  
D. O'Reilly

1986 ◽  
Vol 44 (6) ◽  
pp. 899-906 ◽  
Author(s):  
M G Boosalis ◽  
J T McCall ◽  
L D Solem ◽  
D H Ahrenholz ◽  
C J McClain

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