Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study.

Zinc treatment in liver cirrhosis is known to prevent a number of clinical symptoms. Previous studies have also indicated that Zn has a protective effect on the development of the clinical, biochemical and morphological manifestations of hepatic injury if administered simultaneously with the noxious agent. In this study, the protective effects of zinc treatment against the development of liver cirrhosis have been tested in cirrhotic rats treated by intragastric administration of CCl4. The development of morphological lesions has been investigated by means of standardized and comparable techniques, LM, TEM, SEM, microvascular casts and measurements of liver collagen content by colorimetric determination in paraffin embedded sections. LM and EM observations showed typical morphological features of cirrhosis in all CCl4 treated rats. In the same group of animals, the microvascular casts showed the development of the typical 'perinodular' branching and the various anastomoses of pre and post-sinusoidal vessels. Colorimetric evaluation has shown a significant increase in collagen content after CCl4 treatment. Qualitative and quantitative data of livers of CCl4 treated rats supplemented or not with zinc were significantly similar. In conclusion, zinc treatment influences biochemical parameters, but not the morphology of liver cirrhosis.

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

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.

Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial.

The effect of short-term oral zinc supplementation (zinc sulfate 600 mg/day) on hepatic encephalopathy, was assessed in a double-blind, crossover trial. Fifteen cirrhotic patients with stable, chronic hepatic encephalopathy were randomized to receive either oral zinc or a placebo for 10 days. Following a two-week washout period, these were crossed over to the alternate treatment. Conn's index, which comprises the evaluation of the mental state, asterixis, number connection test, EEG record, and plasma ammonia, was used to score the degree of hepatic encephalopathy, both at the beginning and end of each treatment period. Serum zinc was significantly raised after oral zinc administration and reached the levels observed in cirrhotics without hepatic encephalopathy. Despite this, however, no modification in the parameters included in Conn's index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy.

Zinc and other trace elements in liver cirrhosis.

Alterations in trace element concentrations may be observed in patients with chronic liver disease. Notably, selenium and zinc levels are reduced both in serum and in liver tissue of cirrhotic patients. Low selenium levels have been involved in the pathogenesis of liver damage as this element is important in controlling the levels of toxic oxygen radicals in the cells. Zinc deficiency has been involved in the pathogenesis of a number of clinical findings in chronic liver disease. These include the possible role of zinc deficiency in the pathogenesis of hepatic encephalopathy, by inducing alterations in urea metabolism. In CC14 cirrhotic rats oral zinc supplementation reduces ammonia levels and increases OCT activity in the liver. Oral zinc supplementation has been also proposed in the treatment of cirrhotic patients with chronic hepatic encephalopathy, the results however are not yet conclusive.