Paraoxonase-1 status in patients with hereditary hemochromatosis

Hereditary hemochromatosis (HH) is character- ized by accumulation of iron, oxidative stress, infl amma- tion, and fi brogenesis 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 al- terations in serum PON1 status, PON1 gene polymorphisms, and PON1 hepatic expression in patients with HH. We per- formed 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 PON1 192 and PON1 55 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had signifi cantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8-isoprostane concen- trations (index of oxidative stress). PON1 protein expres- sion in liver tissue was higher in patients and showed stronger staining in hepatocytes surrounding the areas of infl amma- tion. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxi dative stress in hereditary hemochromatosis. —Martinelli, N., A. Garcia-Heredia, H. Roca, N. Aranda, V. Arija, B. Mackness, M. Mackness, F. Busti, G. Aragones, J. Pedro-Botet, F. Pedica, I. Cataldo, J. Marsillach, J. Joven, D. Girelli, and J. Camps. Paraoxonase-1 status in patients with hereditary hemochro- matosis. J. Lipid Res. 2013. 54: 1484-1492.