Control of hepatic copper retention in Texel ram lambs by dietary supplementation with copper antagonists followed by a copper depletion regimen

Two groups of six Texel ram lambs were individually fed a commercial feed concentrate containing, on average, 24 mg Cu and 400 mg Fe kg/dry matter (DM), with (Group A) or without (Group O) three copper-antagonists being: Mo 2, S 3000 and Zn 250 mg/kg, for 96 d to assess their combined effect on hepatic Cu retention (HCR). Concentrate feed allowances increased initially from 1 to 2 kg/d, with 0.1–0.2 kg/d chopped hay, but losses of one lamb from each group led to the restriction of concentrate to 1.4 kg/d with an increase in hay allowance to 0.3 kg/d after 26 d. Lambs were weighed on d 0, 26, 61 and 96 before liver biopsy samples were obtained for Cu analysis. Increases in total liver Cu content during the three consecutive intervals between biopsies were estimated on the assumption that dry livers weighed 5.15 g/kg live weight. Plasma samples were collected weekly for the analysis of Cu concentration and γ-glutamyl transpeptidase (EC 2.3.2.2; GGT) activity. HCR as a fraction of Cu intake (FHCR) was lower in Group A than O (0.056 versus 0.097 ± 0.0152; P<0.01) and tended to decrease with time (P<0.1) but final liver Cu concentrations reached values associated with chronic Cu toxicity of 1069 ± 123.4 and 760 ± 63.2 mg Cu/kg DM in Groups O and A, respectively. Plasma GGT increased more in Group O than in Group A (time × group interaction, P<0.05) to final values of 118 ± 16.4 and 64 ± 10.2 IU/l, respectively, which were both above a normal limit of 44 IU/l. After 96 d, sheep were group fed 1 kg/d of a common depletion regimen based on whole barley grain coated with 3000 mg S/kg and containing 3–5 mg Cu/kg DM. After 22 wks of Cu depletion, all but one lamb had GGT values within a normal range. Liver Cu accretion was reduced by feeding the antagonists, but insufficiently to avoid mild hepato-toxicity, which was resolved upon feeding a grain-based diet low in available Cu.