title: Paraoxonase-1 status in patients with hereditary hemochromatosis.
abstract: Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1) is an enzyme that degrades lipid peroxides. This study investigates the alterations in serum PON1 status, PON1 gene polymorphisms, and PON1 hepatic expression in patients with HH. We performed a case-control study in 77 patients with HH (80.5% men, 22-70 years of age) and 408 healthy individuals (43.1% men, 26-74 years of age). Serum PON1 activities against different substrates and PON1192 and PON155 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had significantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8-isoprostane concentrations (index of oxidative stress). PON1 protein expression in liver tissue was higher in patients and showed stronger staining in hepatocytes surrounding the areas of inflammation. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxidative stress in hereditary hemochromatosis.
authors.affiliation: Department of Medicine, Hospital of Verona, Policlinico G.B. Rossi, Verona, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Anabel
authors.initials: A
authors.lastname: García-Heredia
authors.forename: Helena
authors.initials: H
authors.lastname: Roca
authors.forename: Núria
authors.initials: N
authors.lastname: Aranda
authors.forename: Victoria
authors.initials: V
authors.lastname: Arija
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Michael
authors.initials: M
authors.lastname: Mackness
authors.forename: Fabiana
authors.initials: F
authors.lastname: Busti
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonès
authors.forename: Juan
authors.initials: J
authors.lastname: Pedro-Botet
authors.forename: Federica
authors.initials: F
authors.lastname: Pedica
authors.forename: Ivana
authors.initials: I
authors.lastname: Cataldo
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
mesh_terms: D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics; D001706:Biopsy; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005786:Gene Expression Regulation; D006432:Hemochromatosis / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: C075750:8-epi-prostaglandin F2alpha; D005293:Ferritins; D015237:Dinoprost; D007501:Iron; D043303:Aryldialkylphosphatase