Zinc supplementation decreases hepatic copper accumulation in LEC rat |
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Authors: | Blanca P Esparza Gonzalez Rodolfo Niño Fong Candace J Gibson I Carmen Fuentealba M George Cherian |
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Institution: | (1) Department of Pathology, Faculty of Medicine and Dentistry, University of Western Ontario, N6A 5C1 London, ON, Canada;(2) College of Veterinary Medicine, Western University of Health Sciences, 91766-1854 Pomona, CA |
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Abstract: | The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon
rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given
a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed
at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared
with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats
in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after
12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular
carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic
Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual
mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high
dietary Zn content. |
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Keywords: | Apoptosis copper Long Evans Cinnamon rat metallothionein zinc |
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