Effects of chronic copper exposure during early life in rhesus monkeys
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Background: Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. Objective: The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 ing Cu/L. Design: From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and Cu-67 retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. Results: Cu-67 retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with &AP; 75% in controls at age 2 mo. At age 8 mo, 67 Cu-67 retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 Î¼ g/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 Î¼ g/g at 2 mo in controls. Measurements could not be completed in all animals. Conclusions: No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.