Time-course of changes in hepatic lipid peroxidation and glutathione metabolism in rats with carbon tetrachloride-induced cirrhosis

1. The aims of the present study were to assess: (i) the temporal relations hips between hepatic lipid peroxidation, changes in the glutathione detoxif ication system and the onset/development of cirrhosis in CCl4-treated rats; and (ii) the effects of oral zinc administration on these parameters, 2. Cirrhosis was induced in 120 rats by intraperitoneal injections of CCl4 twice a week over 9 weeks, One hundred and twenty additional animals were u sed as controls. Both groups were further subdivided to receive either a st andard diet or one supplemented with zinc. Subsets of 10 animals each were killed at weeks 1, 2, 3, 5, 7 and 9 from the start of the study. 3. Induction of cirrhosis produced a decrease in the components of the hepa tic glutathione anti-oxidant system: glutathione transferase activity decre ased from Meek 1, the concentration of reduced glutathione (GSH) decreased from week 5 and glutathione peroxidase (GPx) activity decreased from week 7 , This impairment was chronologically related to an increase in fret radica l generation, Hepatic lipid peroxidation was significantly correlated with GPx activity (r = -0.47; P < 0.001) in CCl4-treated rats. Zinc administrati on did not produce any significant improvement of the hepatic glutathione s ystem, 4. In conclusion, cirrhosis induction in rats by CCl4 administration produc ed a decrease in the hepatic glutathione antioxidant system that was relate d to an increase in free radical production. Furthermore, zinc supplementat ion produced a reduction in the degree of hepatic injury and a normalizatio n of lipid peroxidation, but not an improvement of the hepatic GSH anti-oxi dant system.