Suppressive effects of dietary D-penicillamine on the gene expression of hepatic metallothionein-1 and protein level of hepatic metallothionein in Long-Evans Cinnamon rats

Abstract

We investigated the effects of dietary D-penicillamine on copper and zinc contents in the liver, serum, and urine of Long-Evans Cinnamon (LEC) rats, as well as the gene expression of hepatic metallothionein-1 and hepatic metallothionein protein level in these animals. Young male LEC and Fischer rats were fed a basal or D-penicillamine (5 g D-penicillamine/kg diet) diet for 16 days. The urinary output of copper and zinc was markedly increased by the D-penicillamine diet, and the copper and zinc contents in the liver were significantly decreased in LEC rats. Excess copper accumulation in the liver induced hepatic metallothionein in LEC rats, but the D-penicillamine diet depressed the level of hepatic metallothionein-1 mRNA as well as the hepatic metallothionein protein level. When fed the basal diet, serum ornithine carbamoyltransferase activity was higher in LEC rats than in Fischer rats, but a significant decrease in serum ornithine carbamoyltransferase activity rats was observed in LEC rats on feeding the D-penicillamine diet. These results indicated that dietary D-penicillamine significantly reduced excess copper and zinc in the livers of LEC rats through urinary excretion, and the decrease in hepatic copper and zinc contents caused a decrease in the levels of metallothionein-1 mRNA and metallothionein protein in LEC rats.