Possible adverse effect of high δ-alpha-tocopherol intake on hepatic iron overload: Enhanced production of vitamin C and the genotoxin, 8-hydroxy-2′- deoxyguanosine

Excess hepatic iron generates reactive oxygen species that result in oxidative stress and oxidative damage to the liver. Vitamins have hitherto been considered to be a possible remedy. The aim of this study was to determine if high doses of δ-α-tocopherol supplementation in iron overload would ameliorate the oxidative stress. Four groups of 20 male Wistar albino rats were studied: group 1 (control) was fed normal diet, group 2 (Fe) 0.75% Ferrocene iron, group 3 (FV gp) 0.75% Ferrocene/δ-α-tocopherol (10× RDA), group 4 (V gp) normal diet/δ-α-tocopherol. After 12 months, serum iron, reduced glutathione, catalase, vitamin C, Oxygen Radical Absorbance Capacity, lipid peroxidation, 8-hydroxy-2′-deoxyguanosine (8-OHdG), aspartate transaminase (AST), and alanine transaminase (ALT) were measured. Vitamin C levels were: F gp5.04±0.09; FV gp5.85±0.13 (μmol/l) (p<0.05). 8-hydroxy-2′-deoxyguanosine levels were: F gp143.6±6.4; FV gp179.2±18.2 (ng/ml) (p<0.05). Oxidative liver damage, as determined by serum AST and ALT levels, was not attenuated by α-tocopherol. A positive correlation existed between vitamin C and 8-OHdG, suggesting possible δ-α-tocopherol toxicity.