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.