title: The failure of selenium supplementation to prevent copper-induced liver damage in Fischer 344 rats.
abstract: This study evaluates the ability of selenium (Se) supplementation to prevent experimental copper (Cu)-induced hepatocellular damage. Weanling male Fischer 344 rats were randomly assigned to groups of 15, 3 groups (A,B,C) were fed Cu-loaded diets (containing 2000 microg/g copper, added as CuSO4) and different levels of Se (added as Na2SeO3 x 5H2O) as follows: A) Cu-loaded/Se adequate diet (0.4 microg/g Se, fed basis); B) Cu-loaded/Se-supplemented diet (2 microg/g Se); and C) Cu-loaded/Se-deficient diet (< 0.2 microg/g). Three additional groups (D,E,F) were fed diets containing adequate levels of Cu (14 microg/g Cu, fed basis) and different levels of Se as follows: D) Cu-adequate/Se-adequate diet; E) Cu-adequate/Se-supplemented diet (2 microg/g Se); and F) Cu-adequate/Se-deficient (< 0.2 microg/g) diet. After 4, 8, and 12 weeks on the experimental diets, liver samples were processed for histology, histochemistry, metal analysis, glutathione peroxidase (GSH-Px) measurement, and quantification of malondialdehyde (MDA). Morphologic changes characteristic of Cu-associated hepatitis, without an increase in hepatic MDA levels, were seen in all Cu-loaded rats in each sampling. Similar changes occurred in rats fed Se-adequate, Se-supplemented and Se-deficient diets. This study demonstrates that Fischer 344 rats fed 2000 microg/g Cu develop morphologic changes due to Cu toxicity without evidence of lipid peroxidation. Furthermore, Se supplementation does not result in protection against Cu-induced liver injury.
authors.affiliation: Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown.
authors.forename: E M
authors.initials: EM
authors.lastname: Aburto
authors.forename: A
authors.initials: A
authors.lastname: Cribb
authors.forename: I C
authors.initials: IC
authors.lastname: Fuentealba
authors.forename: B O
authors.initials: BO
authors.lastname: Ikede
authors.forename: F S
authors.initials: FS
authors.lastname: Kibenge
authors.forename: F
authors.initials: F
authors.lastname: Markham
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D019587:Dietary Supplements; D005979:Glutathione Peroxidase / Q000032:analysis; D006651:Histocytochemistry / Q000662:veterinary; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D010865:Pilot Projects; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D008315:Malondialdehyde; D003300:Copper; D005979:Glutathione Peroxidase; D012643:Selenium