Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases

Background/Aims: We previously reported that paraoxonase-1 activity measurement may be useful for the evaluation of liver diseases. Because oxidative stress plays a role in liver apoptosis, and lipid peroxides are hydrolyzed by paraoxonase-1, we have extended our studies to explore the relationships between this enzyme and oxidative stress, fibrosis and apoptosis. Methods: We measured paraoxonase-1 activity and concentration, soluble FAS concentration, serum fibrosis markers, and total peroxides in a group of patients with minimal hepatic changes (n = 25), chronic hepatitis (n = 51), or liver cirrhosis (n = 17). We also measured the Knodell activity index in liver biopsies and performed FAS and PON1 immunostaining. Results: Patients with liver diseases showed an increase in soluble FAS, fibrosis markers and paraoxonase-1 concentrations, as well as a decrease in PON1 activity. Paroxonase-1 activity and concentration were correlated with soluble FAS (r = -0.43, P < 0.001 and r = 0.27, P = 0.007, respectively). Paraoxonase-1 concentration showed a significant inverse association with FAS immunostaining (P = 0.013) and a direct association with PON1 immunostaining (P < 0.001). Conclusions: These results suggest an active role of PON1 in the regulation of oxidative stress, fibrosis and hepatic cell apoptosis in chronic liver diseases. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.