Inhibition of hepatic cell nuclear DNA fragmentation by zinc in carbon tetrachloride-treated rats

Background/Aims: The aims of this study were to ascertain: 1) whether hepat ic cell DNA fragmentation is increased in rats with early stages of liver d isease induced by carbon tetrachloride; 2) whether the inhibition of DNA cl eavage is involved in the hepatoprotective effects of zinc; and 3) if relat ionships exist between DNA fragmentation and the onset of fibrosis in this experimental model. Methods: Twenty-one treated rats and 23 controls were divided into two grou ps to receive either a standard diet or one supplemented with zinc, All the animals were sacrificed 1 week later for histological and biochemical asse ssments, which included a DNA fragmentation index, hepatic zinc and metallo thionein concentrations, fibrosis measured by hepatic hydroxyproline concen tration and plasma alanine aminotransferase activity. Results: Hepatic cell DNA fragmentation was increased in rats with early he patic fibrosis and the increase was independent of hepatocytolysis, as meas ured by alanine aminotransferase activity. Oral zinc administration inhibit ed hepatic cell DNA fragmentation in the treated rats and was proportional to the hepatic concentration of the metal. The mechanism of the zinc-mediat ed decrease in DNA cleavage was related to an increase in the hepatic metal lothionein concentration. Hepatic cell DNA fragmentation was related to hyd roxyproline concentration. Conclusions: Our results suggest that apoptosis may be involved in the earl y transformations occurring in the liver and which can lead to the initiati on of cirrhosis, As such, the potential therapeutic use of zinc supplementa tion would warrant further investigation.