Dietary Management of Hepatic Copper Accumulation in Labrador Retrievers

Abstract

Background: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases.Objectives: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations.Animals: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations.Methods: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo.Results: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n 5 21; group 1, P o .001; group 2, P 5 .001) and at recheck 2 (n5 16; group 1, P 5 .03; group 2, P 5 .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P 5 .65), at recheck 1 or at recheck 2 (P 5 .52-.79).Conclusions and Clinical Relevance: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.

Canine models of copper toxicosis for understanding mammalian copper metabolism

“…In some breeds, acute hemolytic crisis due to a massive release of copper into the circulation is recognized. As in humans, treatment with the copper chelators D-penicillamine and 2,3,2-tetramine is effective in decreasing liver copper levels in dogs (Allen et al 1987; Hoffmann et al 2009; Mandigers et al 2005; Twedt et al 1988). Administration of zinc acetate or zinc gluconate is described to have beneficial effects in decoppering and in maintenance therapy (Brewer et al 1992; Hoffmann 2009; Hoffmann et al 2009; Hoogenraad and Rothuizen 1986).…”

“…Copper-accumulating traits in the Labrador retriever show a heritability of up to 85% (Hoffmann et al 2008). Involvement of environmental factors in the disease pathogenesis was proven by the fact that dietary management with a low-copper diet was effective in preventing progression of the disease (Hoffmann et al 2009). Unpublished results demonstrated that the disease is polygenic and the Labrador form of copper storage disease might become a good example of the power of canine populations to resolve complex genetic diseases (J. Rothuizen, personal communication).…”

Acquired Proximal Renal Tubular Dysfunction in 9 Labrador Retrievers with Copper‐Associated Hepatitis (2006–2012)

“…All dogs were fed a low copper diet which has been shown to decrease hepatic copper concentrations in Labradors with CAH. 35 However, gradual reduction by dietary restriction is unlikely to be the sole explanation. All dogs were treated with antioxidants, which potentially could ameliorate the oxidative damage induced by excess tissue copper.…”

Qualidade nutricional de rações para cães: Influência de Zn na absorção de Cu e na prevenção de doença hepática

“…Os valores obtidos para as rações demonstraram uma bioacessibilidade considerável, ou seja, ao menos 50 % do cobre presente provavelmente encontravase sob a forma solúvel em todas as rações. Duas rações para cães adultos classificadas como econômicas apresentaram as maiores concentrações bioacessíveis, com 91 % e 90 %, seguidas das rações do segmento super premium para filhote com 81 % e adulto com 80 %, demonstrando a grande importância das rações na dieta dos cães quanto ao fornecimento desse mineral nas ingestões diárias, principalmente para aquelas raças caninas com predisposição genética a desenvolverem hepatopatias associadas ao acúmulo do cobre (HOFFMANN et al, 2009 Ao menos 32 % das rações para cães adultos e 19 % das rações para filhotes apresentaram valores discrepantes comparados com os valores de referência dos minerais exigidos pela AAFCO.…”

“…O acúmulo de cobre no fígado ocasiona lesões progressivas nas organelas dos hepatócitos, resultando em hepatite crônica e cirrose. Todavia, a administração de zinco na dieta tem sido altamente recomendada para o tratamento dessa doença, devido ao papel passivo do zinco que induz a formação de metalotioneína e impede o transporte de cobre na circulação (HOFFMANN et al, 2009). …”