AbstractThe ability of dietary antioxidants to reduce lipid peroxidation induced by iron overload was examined in weanling male Sprague‐Dawley rats. Animals were fed ad libitum a modified AIN‐76A diet (control) or control diet with 0.5%α‐tocopherol acid succinate, 0.5% crystalline trans‐β‐carotene, or 0.5%α‐tocopherol acid succinate + 0.5% trans‐β‐carotene for four weeks. In the following four‐week period, the animals received the above diets with 10,000μg Fe/g; a control group continued to receive 35μg Fe/g, and a high‐iron group received 10,000μg Fe/g with no antioxidants. After four weeks of dietary supplementation withα‐tocopherol,β‐carotene, orα‐tocopherol +β‐carotene, liver concentrations ofα‐tocopherol andβ‐carotene increased significantly (p<0.001). Liver lipid peroxidation, measured by the lipid‐conjugated diene assay, increased significantly from 0.012μmol/mg of lipid in the controls to 0.021μmol/mg of lipid in animals receiving the high‐iron diet. However, lipid peroxidation was significantly reduced in all animals fed the antioxidants, with the group fedα‐tocopherol +β‐carotene having a lower level than the high‐iron group. Total serum cholesterol was elevated in animals fed a high‐iron diet and in animals fed the high‐iron diet withα‐tocopherol. In contrast, total serum cholesterol levels in the two groups of animals receiving the diets containing high iron withβ‐carotene alone or high iron withβ‐carotene +α‐tocopherol were significantly reduced to the level of the control group. High‐density lipoprotein cholesterol also decreased to baseline in the animals receivingβ‐carotene alone. Modulation of lipid peroxidation byα‐tocopherol orβ‐carotene may be an important mechanism for reducing oxidative stress.