Long-term observation of subclinical chronic copper poisoning in two sheep breeds

Fourteen castrated male sheep of two breeds, the Mutton Merino (MMB) and Blackhead Suffolk cross breed (BSC), were exposed to an oral copper (Cu) intake of 3.7 mg/day per kg body weight for 84 days (high Cu group, HCu), and 11 castrated male sheep received a daily oral Cu intake of 0.16 mg/day per kg body weight (controls). Liver Cu concentration was measured in liver biopsies until 2.7 years after Cu overdose. Haematologic parameters, plasma Cu, enzymes and metabolites were analysed and post-mortem examinations were carried out. No haemolytic crises occurred. The highest liver Cu concentrations (133-677 mg/kg wet weight) were measured in HCu sheep around day 110 with significantly higher values in BSC than in MMB. The very slow decreases of liver Cu concentration of HCu sheep after day 215 showed individual half-life periods of 175 +/- 91 days. A progressive Cu retention in the liver of HCu sheep during Cu supplementation indicates strong Cu binding and storage in the liver. High values of glutamate dehydrogenase (20-940 U/l) measured frequently until day 700 and a diminished plasma clearance of bromosulphthalein as well as pathohistological findings of focal liver necrosis confirm the markedly chronic character of Cu poisoning.