Genetic hemochromatosis and Wilson'S disease: Role for oxidant stress?

Robert S Britton; Kyle E Brown

doi:10.1002/hep.1840210445

Hereditary haemochromatosis is characterised by iron overload that may lead to tissue damage. Free iron is a potent promoter of hydroxyl radical formation that can cause increased lipid peroxidation and depletion of chain‐breaking antioxidants. We have therefore assessed lipid peroxidation and antioxidant status in 15 subjects with hereditary haemochromatosis and age/sex matched controls. Subjects with haemochromatosis had increased serum iron (24.8 (19.1–30.5) vs. 17.8 (16.1–19.5) μmol/L, P = 0.021) and % saturation (51.8 (42.0–61.6) vs. 38.1 (32.8–44.0), P = 0.025). Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were increased in haemochromatosis (0.59 (0.48–0.70) vs. 0.46 (0.21–0.71) μmol/l, P = 0.045), and there were decreased levels of the chain‐breaking antioxidants alpha‐tocopherol (5.91 (5.17–6.60) vs. 7.24 (6.49–7.80) μmol/mmol cholesterol, P = 0.001), ascorbate (51.3 (33.7–69.0) vs. 89.1 (65.3–112.9), P = 0.013), and retinol (1.78 (1.46–2.10) vs. 2.46 (2.22–2.70) μmol/l, P ‐ 0.001). Patients with hereditary haemochromatosis have reduced levels of antioxidant vitamins, and nutritional antioxidant supplementation may represent a novel approach to preventing tissue damage. However, the use of vitamin C may be deleterious in this setting as ascorbate can have prooxidant effects in the presence of iron overload. The RRR‐alpha‐tocopherol (vitamin E) content in plasma from 46 patients with liver diseases and 23 healthy controls was determined by high performance liquid chromatography and electrochemical detection. Patients were divided into three groups: alcoholic liver diseases (n = 17; group A), hemochromatosis (n 17;group B) and Wilson's disease (n 12;group C). Lipidstandardized alpha‐tocopherol levels were determined to neutralize differences due to hyperlipemia. The ratio of serum vitamin E to serum lipids (cholesterol, triglycerides, phospholipids) was highest in healthy controls and in patients in group A with cirrhosis and normal transaminases and bilirubin. Patients in group A with acute or chronic ethanol intoxication and high bilirubin levels had a 37% lower lipid‐standardized vitamin E level than controls. Patients in group B with hemochromatosis, showing high serum iron (>180 μg/dl), a low free iron binding capacity (<8 μmol/l) and high ferritin‐levels (>450 μg/l), had a 34% lower vitamin E/lipid ratio than healthy controls. No significant lowering of the vitamin E/lipid ratio was observed in the other patients in group B. A significant decrease (37%) in the vitamin E/lipid ratio was only detectable in patients with Wilson's disease (group C) showing high free serum copper (>10 μg/dl). The data support a role for free radicals in the pathogenesis of active liver diseases. © Journal of Hepatology.

Genetic hemochromatosis and Wilson'S disease: Role for oxidant stress?

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