Michael E. Callender

ANTIOXIDANT STATUS AND LIPID PEROXIDATION IN HEREDITARY HAEMOCHROMATOSIS

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) mumol/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) mumol/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) mumol/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) mumol/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.

Zinc Absorption in Alcoholics Using Zinc-65

Alcoholism is occasionally complicated by zinc deficiency. We have assessed the possibility that malabsorption of zinc may be a potential cause. Using a dual isotope absorption technique the absorption of 65Zn in 18 alcoholic patients was 37% (13 +/- SD) and 56% (10 +/- SD) in a normal control group (p less than 0.001). The mean serum zinc in 55 alcoholic patients was 11.6 mumol/l (3.0 +/- SD) and in 36 normal volunteers the mean serum zinc was 13.6 mumol/l (1.8 +/- SD; p less than 0.001). This study suggests that chronic alcohol abuse will decrease the absorption of zinc and this may contribute towards the zinc deficiency occasionally associated with alcoholism.

Trace elements and alcohol

In our study alcoholic patients with and without cirrhosis have a decreased serum zinc. They also have increased serum copper and iron with an increase in the serum ferritin. There is no evidence of selenium deficiency in either alcoholic group. Alcohol when given with zinc in a single dose to normal volunteers increases the serum zinc and therefore appears to increase the absorption of zinc.

Metal Analysis of Human Liver as an Aid to Diagnosis

A simple procedure for the direct estimation of Fe, Zn and Cu in fresh human liver obtained by percutaneous sampling has been developed. After drying, the sample of 3–5 mg is dissolved in nitric acid to give approximately 2 mg/ml. Fe and Zn are measured by flame atomic absorption and Cu in a graphite furnace.

Serum zinc and venous occlusion.

Serum zinc was measured with and without venous occlusion in 100 subjects. During venous occlusion serum zinc was 0.79 ug/ml and without venous occlusion it was 0.75 ug/ml (p less than 0.001).

The effect of alcohol on zinc absorption : Studies using rat small intestinal perfusion.

Two methods of intestinal perfusion are described and used to study the effecs of alcohol on zinc absorption in the rat small intestine. The first method used perfusion of the lumen of the rat small intestinein situ without interruption of the vascular supply. During perfusion with a zinc-containing medium (with and without alcohol), alcohol was found to have no effect on net zinc uptake from the lumen of the intestine. However, there were significantly higher serum zinc concentrations recorded in the rats perfused wih the zinc and alcohol, 28.8 μmol/L, when compared with a group perfused without alcohol, 19.1 μmol/L (P < 0.01). The second method used simultaneous perfusion of the lumen of the rat small intestine, with constant-rate perfusion of the vascular bed with an artificial blood supply. In this experiment with a zinc-containing medium, with and without alcohol, there was no difference noted in zinc absorption from the lumen of the intestine, or release into the artificial blood supply. Therefore, in conclusion, alcohol does not appear to directly influence zinc absorption by the mucosal cells of the small intestine.