Copper Components and Ferroxidase of Blood Plasma of Dogs, a species prone to Liver Toxicosis
Mentor:Maria Linder, Professor of Biochemistry, California State University, Fullerton
Dogs have much higher liver copper concentrations than most other mammals, their rate of copper excretion being much lower. As a result, dogs tend to develop hepatitis, an inflammation of the liver also involving formation of reactive oxygen species, which can lead to liver failure and death. Dogs are also unique in having a form of albumin in their blood with low affinity for copper. We hypothesized the that high hepatic copper and low affinity for copper in albumin are related, and that analysis of blood plasma would reveal indicators to be used for diagnosis of their disease. Plasma samples from Labrador retrievers with high and normal liver copper were obtained from Dr. Hille Fieten (Utrecht University, Holland). Other variables were hepatitis and mutation of a specific gene hypothesized responsible for the high copper. Total plasma copper determined by atomic absorption, ferroxidase activity, and profiles of copper components obtained by size exclusion chromatography on Superdex 200 were measured. The plasma copper profiles had five consistent copper components, eluting in fractions 20-25 (probably macroglobulin/transcuprein), 27-29 (ceruloplasmin), 31-34 (albumin and possibly hephaestin), and 40-43 (a low molecular weight component of unknown nature). The latter was prominent in dogs with hepatitis. In dogs with high liver copper, the transcuprein and albumin/hephaestin portion of the profiles appeared to be increased. Total plasma copper were similar for the different groups, except that dogs with the affected gene mutation had a significantly lower levels (p<0.001). There were no differences in ferroxidase activity (an activity of ceruloplasmin) except for those with the mutated gene, which had increased. We conclude that the mutated gene leads to changes in total copper and ferroxidase expression in the plasma, and that components of about 700, 70kDa and low molecular weight (to be identified) may be indicative of liver copper and hepatitis.