, Volume 18, Issue 5, pp 541–551 | Cite as

Early Histological and Functional Effects of Chronic Copper Exposure in Rat Liver

  • Felipe A. Cisternas
  • Gladys Tapia
  • Miguel Arredondo
  • Denise Cartier-Ugarte
  • Pamela Romanque
  • Walter D. Sierralta
  • María T. Vial
  • Luis A. Videla
  • Magdalena Araya


Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O2 consumption and colloidal carbon-induced O2 uptake in Cu-treated rats, with enhanced carbon-induced O2/carbon uptake ratios and NF-κB DNA binding activity. These changes were time-dependent and returned to control values after 12 or16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-κB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.


copper Küpffer cells liver damage oxidative stress rats 


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Copyright information

© Springer 2005

Authors and Affiliations

  • Felipe A. Cisternas
    • 1
  • Gladys Tapia
    • 2
  • Miguel Arredondo
    • 1
  • Denise Cartier-Ugarte
    • 2
  • Pamela Romanque
    • 2
  • Walter D. Sierralta
    • 1
  • María T. Vial
    • 3
  • Luis A. Videla
    • 2
  • Magdalena Araya
    • 1
  1. 1.Instituto de Nutrición y Tecnología de los AlimentosUniversidad de ChileMacul, SantiagoChile
  2. 2.Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de MedicinaUniversidad de ChileChile
  3. 3.Unidad de Anatomía PatológicaHospital San Borja ArriaránSantiagoChile

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