Hepatic copper accumulates in ferrets with and without hepatobiliary disease

Julianne N. Richard Department of Clinical Sciences, Cummings School of Veterinary Medicine, North Grafton, MA

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Jennifer E. Graham Department of Clinical Sciences, Cummings School of Veterinary Medicine, North Grafton, MA

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Sharon A. Center Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY

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Michael M. Garner Northwest ZooPath, Monroe, WA

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Drury R. Reavill Zoo/Exotic Pathology Service, Citrus Heights, CA

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Abstract

OBJECTIVE

To determine hepatic copper concentrations and zonal distribution in ferrets with and without hepatobiliary disease, validate rhodanine-based qualitative copper scoring and digital copper quantification in ferret hepatic samples, and ascertain whether clinical features predicted copper accumulation.

ANIMALS

34 ferrets, including 7 with necroinflammatory disease, 5 with hepatocellular carcinoma, 13 with non-necroinflammatory disease, and 9 with no hepatobiliary disease.

PROCEDURES

Rhodanine-based digital copper quantification was validated by use of liver dually measured by atomic absorption spectroscopy and digital scanning (R 2 = 0.98). Clinical features and hepatic copper scores and concentrations (dry weight liver) were compared between groups. Zonal copper distribution was determined.

RESULTS

Hepatic copper concentration was strongly correlated with copper scores (ρ = 0.88). Ferrets with hepatobiliary disease were significantly older and had significantly higher serum alkaline phosphatase and γ-glutamyltransferase activities and creatinine concentrations. Centrilobular copper accumulated in 23 of 34 (64%) ferrets with (n = 15) and without (8) hepatobiliary disease. Median copper concentrations were not significantly different between ferrets with and without hepatobiliary disease but were significantly higher within neoplastic hepatic tissue in ferrets with hepatocellular carcinoma. Hepatic copper concentrations exceeded feline (> 180 µg/g) and canine (> 400 µg/g) reference limits in 19 and 9 ferrets, respectively. Hepatic copper > 1,000 µg/g occurred in 5 ferrets with and 2 without hepatobiliary disease. Clinical features did not predict copper accumulation.

CLINICAL RELEVANCE

Rhodanine-based digital copper quantification and qualitative copper scoring discerned liver copper accumulation in ferrets. Ferrets with and without hepatobiliary disease displayed a propensity for centrilobular hepatic copper accumulation of uncertain clinical importance. Clinical and clinicopathologic features could not exclusively implicate pathologic copper accumulation.

Abstract

OBJECTIVE

To determine hepatic copper concentrations and zonal distribution in ferrets with and without hepatobiliary disease, validate rhodanine-based qualitative copper scoring and digital copper quantification in ferret hepatic samples, and ascertain whether clinical features predicted copper accumulation.

ANIMALS

34 ferrets, including 7 with necroinflammatory disease, 5 with hepatocellular carcinoma, 13 with non-necroinflammatory disease, and 9 with no hepatobiliary disease.

PROCEDURES

Rhodanine-based digital copper quantification was validated by use of liver dually measured by atomic absorption spectroscopy and digital scanning (R 2 = 0.98). Clinical features and hepatic copper scores and concentrations (dry weight liver) were compared between groups. Zonal copper distribution was determined.

RESULTS

Hepatic copper concentration was strongly correlated with copper scores (ρ = 0.88). Ferrets with hepatobiliary disease were significantly older and had significantly higher serum alkaline phosphatase and γ-glutamyltransferase activities and creatinine concentrations. Centrilobular copper accumulated in 23 of 34 (64%) ferrets with (n = 15) and without (8) hepatobiliary disease. Median copper concentrations were not significantly different between ferrets with and without hepatobiliary disease but were significantly higher within neoplastic hepatic tissue in ferrets with hepatocellular carcinoma. Hepatic copper concentrations exceeded feline (> 180 µg/g) and canine (> 400 µg/g) reference limits in 19 and 9 ferrets, respectively. Hepatic copper > 1,000 µg/g occurred in 5 ferrets with and 2 without hepatobiliary disease. Clinical features did not predict copper accumulation.

CLINICAL RELEVANCE

Rhodanine-based digital copper quantification and qualitative copper scoring discerned liver copper accumulation in ferrets. Ferrets with and without hepatobiliary disease displayed a propensity for centrilobular hepatic copper accumulation of uncertain clinical importance. Clinical and clinicopathologic features could not exclusively implicate pathologic copper accumulation.

Supplementary Materials

    • Supplementary Table S1 (PDF 156 KB)

Contributor Notes

Corresponding author: Dr. Center (sac6@cornell.edu)
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