Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis

Relationships between hepatic antioxidant paraoxonase (PON1) activity, lipi d peroxidation, and liver injury were investigated in rats with CCl4-induce d cirrhosis. The study was performed in 60 CCl4-treated rats and 60 control animals receiving a standard diet or one supplemented with zinc. Subsets o f 10 animals each were killed at weeks 1, 5, and 7 of the study. Results sh owed that PON1 significantly decreased in rats given CCl4 alone compared wi th control animals. This effect was partially reversed in animals receiving zinc. Conversely, lipid peroxides were significantly increased in rats giv en CCl4 alone and returned to approximately normal values in animals receiv ing zinc supplement. PON1 was inversely correlated with lipid peroxidation in all the animals studied. These alterations coincided with changes in ser um alanine aminotransferase activity. In vitro incubation of isolated micro somes with CCl4 or malondialdehyde did not produce any significant changes in PON1, indicating that the decrease in PON1 in CCl4-treated animals was n ot secondary to a direct inhibitory effect of lipid peroxidation products. These data show a time course and quantitative relationship between PON1 ac tivity and lipid peroxidation in rats with CCl4-induced cirrhosis and sugge st that this enzyme plays a significant role within the antioxidant systems in liver microsomes. Copyright (C) 2001 by W.B. Saunders Company.