Association of Dietary Copper and Zinc Levels with Hepatic Copper and Zinc Concentration in Labrador Retrievers

Abstract

Background: Copper-associated hepatitis is an inherited disease in the Labrador Retriever. Apart from genetic factors, dietary intake of copper and zinc are suspected to play a role in the pathogenesis.Objectives: To investigate whether dietary copper and zinc levels of commercially available dry diets are associated with hepatic copper and zinc concentrations in Labrador Retrievers.Animals: Fifty-five Labrador Retrievers that were fed a single brand and type of commercial dry food for at least 1 year. Of these, 44 dogs were family members of Labrador Retrievers with copper-associated hepatitis.Methods: Liver biopsies, blood samples, and diet samples were obtained. Liver specimens were scored histologically and copper and zinc concentrations were quantified. Dietary concentrations of copper and zinc were measured. The association between dietary intake of copper and zinc and hepatic copper and zinc concentrations was investigated by linear regression analysis.Results: High dietary copper and low dietary zinc levels were significantly associated with high hepatic copper levels. No association between dietary intake and hepatic zinc was present.Conclusions and Clinical Relevance: Dietary copper and zinc at current levels in commercially available dry dog food can influence hepatic copper and can be a risk factor for the development of copper-associated hepatitis in Labrador Retrievers with a genetic susceptibility to copper.

Sensitivity and Specificity of PlasmaALT,ALP, and Bile Acids for Hepatitis in Labrador Retrievers

“…Copper‐associated hepatitis is one of the most common forms of primary hepatitis in dogs as shown by a study conducted in 101 purebred and crossbred dogs in the Netherlands, of which up to 36% of the CH and 24% of the AH cases were copper‐associated. 1 The Labrador retriever is a dog breed known to be affected with hereditary copper‐associated hepatitis, influenced by environmental factors such as dietary copper intake . In the current study, increased hepatic copper concentrations were present in Labrador retrievers with different histologic diagnosis, including histologically normal liver, but concentrations were highest in dogs with AH.…”

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

“…The most common toxic injury causing CH in dogs is a consequence of hepatic copper (Cu) excess . Copper‐associated CH (CuCH) may develop in any breed, including mixed breeds, but the Bedlington Terrier (BT), Dalmatian, Labrador Retriever (LR), Doberman Pinscher, and West Highland White Terrier are predisposed.…”

“…The increasing frequency of CH cases beginning in the late 1990s correlates with the change in the premixes used to supplement Cu in commercial dog foods, which resulted in higher amounts of bioavailable Cu in diets . The panel believes that the National Research Council (NRC) and Association of American Feed Control Officials dietary guidelines, along with a change to more bioavailable Cu chelate premixes in commercial dog food, are linked with an increased prevalence of hepatic Cu accumulation in dogs (Table ) .…”

“…The panel believes that the National Research Council (NRC) and Association of American Feed Control Officials dietary guidelines, along with a change to more bioavailable Cu chelate premixes in commercial dog food, are linked with an increased prevalence of hepatic Cu accumulation in dogs (Table ) . The Cu concentrations in dog foods often exceed NRC recommendations by >2‐4 …”

Gene expression patterns in the progression of canine copper-associated chronic hepatitis

“…Recently two missense mutations in copper transporters ATP7B (Wilson disease gene) and ATP7A (Menkes disease gene) that were respectively positively and negatively associated to hepatic copper levels were identified in Labrador retrievers[28]. Besides a genetic background, hepatic copper concentrations in Labrador retrievers are also influenced by dietary copper intake[32], exemplifying the similarities with both Wilsons disease and non-Wilsonian ecogenetic forms of human copper toxicosis. Affected Labrador retrievers accumulate copper in their livers and can reach copper levels of over 4,000 mg/kg dry weight liver[33,34], whereas normal copper levels in dog liver are < 400 mg/kg dry weight liver (dwl)[35].…”