Effects of chronic copper exposure during early life in rhesus monkeys

• Published in: The American journal of clinical nutrition Vol. 81; no. 5; pp. 1065 - 1071
• Main Authors: Araya, M, Kelleher, S.L, Arredondo, M.A, Sierralta, W, Vial, M.T, Uauy, R, Lonnerdal, B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.05.2005; American Society for Clinical Nutrition, Inc
• Subjects: Administration, Oral; animal models; Animals; Animals, Newborn; Biological and medical sciences; Copper; Copper - administration & dosage; Copper - metabolism; Copper - pharmacology; copper load; dietary minerals; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; histochemistry; homeostasis; intestinal absorption; Liver; Liver - drug effects; Liver - enzymology; Liver - pathology; liver function; Liver Function Tests; Macaca mulatta; Monkeys & apes; neonates; nutrient excess; nutrient intake; nutrient retention; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Digestive system; Liver; Monkey; neonate monkeys; rhesus monkey; Vertebrata; Chronic; copper absorption; Mammalia; Absorption; Animal; Copper load; Primates; Early; Copper
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/81.5.1065

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 equal to 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 microgram/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microgram/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.