Effects of chronic copper exposure during early life in rhesus monkeys

Araya, M; Kelleher, SL; Arredondo, MA; Sierralta, W; Vial, MT; Uauy, R; Lonnerdal, B; (2005) Effects of chronic copper exposure during early life in rhesus monkeys. The American journal of clinical nutrition, 81 (5). pp. 1065-71. ISSN 0002-9165

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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 mg 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 67Cu 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: 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu 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 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/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.

Item Type: Article
Keywords: Administration, Oral, Animals, Animals, Newborn, Copper, Liver, Liver Function Tests, Macaca mulatta, Research Support, Non-U.S. Gov't
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 15883430
Web of Science ID: 229046300018
URI: http://researchonline.lshtm.ac.uk/id/eprint/12851


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