Effect of age and sex on liver damage due to excess dietary copper in Fischer 344 rats

Objective: The aim of this study was to investigate the morphologic and bio chemical effects of excess dietary copper in young and adult rats of differ ent sex. Methods: Adult Fischer 344 male and female rats were given a diet containing 1500 ppm copper for 18 weeks. Young male and female rats were fe d a similar copper-loaded diet from birth until 16 weeks of age, Age- and s ex-matched control rats were fed a normal rodent diet (<10 ppm copper), Ser um liver enzyme activity was determined in all rats. Livers were sampled fo r histology, histochemistry (rhodanine), immunohistochemical detection of m etallothionein and copper analysis by atomic absorption spectrophotometry, Hepatic metallothionein and zinc concentrations were measured in adult rats . Results: Excess dietary copper caused substantial liver injury, as eviden ced by morphologic changes and increased activity of serum ALT, GGT, and SD H, All copper-loaded rats had significantly (p< 0.05) increased hepatic cop per concentrations compared to controls. However, young copper-loaded rats accumulated more hepatic copper, had more severe liver changes, and had hig her serum liver enzyme activities than adult rats. Histologic changes in co pper-loaded rats consisted of multifocal hepatitis and widespread single-ce ll necrosis, Cytoplasmic copper was detected histochemically in centroacina r zone 1 (portal) and midzone in copper-loaded rats, Immunoreactivity for m etallothionein was prominent in necrotic hepatocytes and within inflammator y foci in copper-loaded rats. However, differences in hepatic metallothione in concentrations were not detected between adult copper-loaded and control rats. Conclusions: Young Fischer 344 rats are more susceptible than adults to copper-induced liver injury.