Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases.
OBJECTIVE
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.
Ferré
Natàlia
N
DNA Unit, Centre de Diagnòstic Biomèdic, IDIBAPS, Hospital Clínic Universitari,C. Villarroel 170, 08036-Barcelona, Spain.
Marsillach
Judit
J
Camps
Jordi
J
Mackness
Bharti
B
Mackness
Michael
M
Riu
Francesc
F
Coll
Blai
B
Tous
Mònica
M
Joven
Jorge
J
D000328:Adult; D017209:Apoptosis; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000145:classification / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015203:Reproducibility of Results; D019014:fas Receptor / Q000235:genetics*
D019014:fas Receptor; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human