The Antioxidant and Hepato-Protective Effects of Zinc are Related to Hepatic Cytochrome P450 Depression and Metallothionein Induction in Rats with Experimental Cirrhosis

Abstract

The aim of the present study was to investigate the time-course of changes in hepatic lipid peroxidation, cytochrome P450 and metallothionein concentrations, and superoxide dismutase and catalase activities in relation to the onset and development of cirrhosis in CCl4-treated rats. Further, the effects of oral zinc administration on these parameters were assessed. Cirrhosis was induced in 120 rats by intraperitoneal injections of CCl4 twice weekly over 9 weeks. Controls were 120 additional animals. Both groups were further subdivided to receive either a standard diet or one supplemented with zinc. Subsets of 10 animals each were euthanized at weeks 1, 2, 3, 5, 7 and 9 from the start of the study. Results indicated that zinc administration delayed the cirrhotic process and the increase in lipid peroxidation. These changes, consistently maintained during the first 5 weeks of the study, were associated with a significant decrease in the hepatic concentration of cytochrome P450 and an increase in the hepatic concentration of metallothioneins. Zinc supplementation did not produce any significant change in superoxide dismutase and catalase activities. These results suggest that cytochrome P450 and metallothioneins may play an important role in the hepato-protective effects of zinc against lipid peroxidation in experimental cirrhosis.