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.
Highlights
Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue
PON1 gene and protein expressions are observed in many cell types [10, 11], and the enzyme is found in the circulation bound to high-density lipoproteins (HDL) [12]
The present study shows that hepatic PON1 protein expression is clearly increased in HH patients
Summary
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. The protective capacity of ferritin is overwhelmed in HH, hepatic oxidative stress and fibrogenesis being characteristic of this disorder [3, 4] In this setting, research on liver protection by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1), an enzyme with lactonase and esterase activities, degrades lipid peroxides [6,7,8] and plays an important role in the intracellular antioxidant system [9].
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