Effect of chronic exposure to excess dietary copper and dietary selenium supplementation on liver specimens from rats.
OBJECTIVE
To determine the effects of chronic exposure to excess dietary copper (Cu) on liver specimens from rats and the effects of dietary selenium (Se) supplementation in experimental Cu toxicosis.


METHODS
60 weanling male Fischer 344 rats.


METHODS
Rats were randomly assigned to 4 groups of 15 rats each and fed 1 of the following 4 diets: high Cu (500 microg/g)/adequate Se (0.2 microg/g); high Cu (500 microg/g)/supplemented Se (2 microg/g); adequate Cu (18 microg/g)/adequate Se (0.2 microg/g); or, adequate Cu (18 microg/g)/supplemented Se (2 microg/g). Five rats per group were euthanatized after 3, 6, and 12 months, and liver specimens were obtained for histologic examination, histochemistry, metal analysis by atomic absorption spectrophotometry, measurement of glutathione peroxidase activity, and assessment of lipid peroxidation, using quantification of malondialdehyde (MDA) by the thiobarbituric acid reaction.


RESULTS
Hepatic Cu concentration was significantly higher in rats fed high Cu diets (range, 9 to 18 microg/g of tissue [wet weight]), compared with rats receiving adequate Cu diets (4.0 to 5.7 microg/g of tissue). Rats fed high-Cu diets for 3, 6, and 12 months had mild multifocal hepatitis often surrounding necrotic foci. However, an increase in hepatic MDA content, indicative of lipid peroxidation, was not detected in these rats. Development of morphologic changes was not prevented by use of dietary Se supplementation.


CONCLUSIONS
Long-term exposure to excess dietary Cu caused mild hepatic lesions in Fischer 344 rats. Dietary Se supplementation did not prevent hepatic damage in rats with Cu toxicosis.
Aburto
E M
EM
Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
Cribb
A E
AE
Fuentealba
C
C
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003300:Copper / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019587:Dietary Supplements; D005979:Glutathione Peroxidase / Q000378:metabolism; D006651:Histocytochemistry; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D008315:Malondialdehyde; D003300:Copper; D005979:Glutathione Peroxidase; D012643:Selenium