Early histological and functional effects of chronic copper exposure in rat liver.
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 1,200 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 O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 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-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.
Cisternas
Felipe A
FA
Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, José Pedro Alessandri 5540, Macul, Santiago 11, Chile. maraya@inta.cl
Tapia
Gladys
G
Arredondo
Miguel
M
Cartier-Ugarte
Denise
D
Romanque
Pamela
P
Sierralta
Walter D
WD
Vial
María T
MT
Videla
Luis A
LA
Araya
Magdalena
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019327:Copper Sulfate / Q000493:pharmacokinetics / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D006651:Histocytochemistry; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D016328:NF-kappa B; D004247:DNA; D019327:Copper Sulfate; D010100:Oxygen