Possible adverse effect of high delta-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 delta-alpha-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/delta-alpha-tocopherol (10x RDA), group 4 (V gp) normal diet/delta-alpha-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 gp = 5.04 +/- 0.09; FV gp = 5.85 +/- 0.13 (micromol/l) (p < 0.05). 8-hydroxy-2'-deoxyguanosine levels were: F gp = 143.6 +/- 6.4; FV gp = 179.2 +/- 18.2 (ng/ml) (p < 0.05). Oxidative liver damage, as determined by serum AST and ALT levels, was not attenuated by alpha-tocopherol. A positive correlation existed between vitamin C and 8-OHdG, suggesting possible delta-alpha-tocopherol toxicity.
Asare
George A
GA
MRC/Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa. gasare@chs.edu.gh
Ntombini
Bicky
B
Kew
Michael C
MC
Kahler-Venter
Christina P
CP
Nortey
Ezekiel N
EN
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity*; D001205:Ascorbic Acid / Q000097:blood / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D005296:Ferrous Compounds; D005978:Glutathione / Q000097:blood; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D000075163:Metallocenes; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation; D014815:Vitamins / Q000008:administration & dosage / Q000633:toxicity*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000633:toxicity*
D000975:Antioxidants; D015415:Biomarkers; D005296:Ferrous Compounds; D000075163:Metallocenes; D014815:Vitamins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007501:Iron; D002374:Catalase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine; D005978:Glutathione; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; C004998:ferrocene