The failure of selenium supplementation to prevent copper-induced liver damage in Fischer 344 rats

This study evaluates the ability of selenium (Se) supplementation to preven t experimental copper (Cu)-induced hepatocellular damage. Weanling male Fis cher 344, rats were randomly assigned to groups of 15, 3 groups (A,B,C) wer e fed Cu-loaded diets (containing 2000 mug/g copper, added as CuSO4) and di fferent levels of Se (added as Na2SeO3. 5H(2)O) as follows: A) Cu-loaded/Se adequate diet (0.4 mug/g Se, fed basis); B) Cu-loaded /Se-supplemented die t (2 mug/g Se); and C) Cu-loaded/Se-deficient diet (< 0.2 <mu>g/g). Three a dditional groups (D,E,F) were fed diets containing adequate levels of Cu (1 4 mug/g Cu, fed basis) and different levels of Se as follows: D) Cu-adequat e/Se-adequate diet; E) Cu-adequate/Se-supplemtented diet (2 mug/g Se); and F) Cu-adequate/Se-deficient (< 0.2 <mu>g/g) diet. After 4, 8, and 12 weeks on the experimental diets, liver samples were processed for histology, hist ochemistry, metal analysis, glutathione peroxidase (GSH-Px) measurement, an d quantification of malondialdehyde (MDA). Morphologic changes characterist ic of Cu-associated hepatitis, without an increase in hepatic MDA levels, w ere seen in all Cu-loaded rats in each sampling. Similar changes occurred i n rats fed Se-adequate, Se-supplemented and Se-deficient diets. This study demonstrates that Fischer 344 rats fed 2000 mug/g Cu develop morphologic ch anges due to Cu toxicity without evidence of lipid peroxidation. Furthermor e, Se supplementation does not result in protection against Cu-induced live r injury.