title: Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases.
abstract: 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.
authors.affiliation: DNA Unit, Centre de Diagnòstic Biomèdic, IDIBAPS, Hospital Clínic Universitari,C. Villarroel 170, 08036-Barcelona, Spain.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Ferré
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Michael
authors.initials: M
authors.lastname: Mackness
authors.forename: Francesc
authors.initials: F
authors.lastname: Riu
authors.forename: Blai
authors.initials: B
authors.lastname: Coll
authors.forename: Mònica
authors.initials: M
authors.lastname: Tous
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
mesh_terms: 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*
chemical_list: D019014:fas Receptor; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human