title: Effects of chronic copper exposure during early life in rhesus monkeys.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile. maraya@inta.cl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Araya
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Kelleher
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Arredondo
authors.forename: Walter
authors.initials: W
authors.lastname: Sierralta
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Vial
authors.forename: Ricardo
authors.initials: R
authors.lastname: Uauy
authors.forename: Bo
authors.initials: B
authors.lastname: Lönnerdal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D003300:Copper / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests; D008253:Macaca mulatta
chemical_list: D003300:Copper