Assessment of copper accumulation in archived liver specimens from cats

Abstract

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.

Assessment of the intracellular distribution of copper in liver specimens from cats

“…Previous studies of hepatic copper concentrations in cats found a wide range of hepatic copper concentrations in healthy control cats and cats without hepatobiliary diseases (e.g., 9.5–451.6 μg/g dry weight liver in 23 cats and 10.8–394.8 μg/g dry weight liver in 47 cats) [ 30 , 31 ]. We previously found copper concentrations greater than the ULRI in cat liver tissue submitted to a US-based veterinary laboratory even when hepatic lesions were not appreciated [ 15 ].…”

“…Tissue sections were stained with hematoxylin and eosin (H&E) for histopathological analysis. Tissue specimens were classified based on previously published criteria of inflammation, lipid accumulation, and the presence of neoplastic cells [ 15 ]. The scoring system and classification criteria are described in S1 and S2 Tables.…”

Evaluation of iron, copper and zinc concentrations in commercial foods formulated for healthy cats

“…[30][31][32][33] Similar to dogs, 7 Cu can accumulate in the tissue of cats, especially the kidney and liver. 3,4 In addition, the amount of dietary Cu correlated with tissue concentrations in cats and concentrations in the liver of cats reflect dietary intake. 6,34 Therefore, the lack of defined maximum regulatory standards in commercial cat foods raises concern for potentially high dietary intakes with consequential accumulation of these trace minerals.…”

“…Conversely, high intake can reduce bioavailability of other nutrients (eg, Zn interferes with Cu absorption) or might lead to accumulation in tissues of cats, especially the kidney and liver. 3–6…”

COMMD1 Exemplifies the Power of Inbred Dogs to Dissect Genetic Causes of Rare Copper-Related Disorders

“…Copper-induced chronic hepatitis in a European short was presented a decade later [112] (Meertens 2005). The levels of copper, and some other trace elements in feline livers were described by various groups [113][114][115][116] (Andreani 2010; Whittemore 2012; Passlack 2014; Yamkate 2020). In addition to house cats (Felis catus), copper levels in other felidae were measured, including bobcats, tigers, cougars, coyotes, and lions [117][118][119] (Bernard 2015; Thomason 2016), Hough 2020.…”