Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis

Hepatology. 1992 Sep;16(3):785-9. doi: 10.1002/hep.1840160326.


Zinc deficiency is common in cirrhosis and may be involved in the alteration of ammonia metabolism. Rats with carbon tetrachloride-induced cirrhosis have high plasma ammonia and low serum and tissue zinc levels. We used this model to examine the effects of oral zinc supplementation on activities of plasma ammonia and liver ornithine transcarbamylase (a key enzyme in the urea cycle). These parameters were examined in two consecutive experiments. Each experiment included two groups of rats treated with carbon tetrachloride; one group received zinc in the drinking water during the induction of cirrhosis, and another served as a control group. Regardless of zinc supplementation, all carbon tetrachloride-treated rats exhibited similar micronodular cirrhosis, with similar histological appearance and liver function impairment. Cirrhotic rats without zinc supplementation showed high plasma ammonia and low serum and hepatic zinc levels and reduced liver ornithine transcarbamylase activity. Serum, hepatic zinc and liver ornithine transcarbamylase activity increased significantly in the zinc-supplemented group, and these rats' plasma ammonia levels became normal. Plasma ammonia level was significantly inversely correlated with liver ornithine transcarbamylase activity and positively correlated with serum and hepatic zinc content. Our results suggest that zinc deficiency may modify hepatic ornithine transcarbamylase activity and, therefore, ammonia disposal.

MeSH terms

  • Administration, Oral
  • Ammonia / blood*
  • Animals
  • Carbon Tetrachloride
  • Liver / enzymology*
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / enzymology*
  • Male
  • Ornithine Carbamoyltransferase / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Zinc / administration & dosage*
  • Zinc / deficiency


  • Ammonia
  • Carbon Tetrachloride
  • Ornithine Carbamoyltransferase
  • Zinc