Doxorubicin (DXR) is an anthracycline antibiotic, broady used in tumor therapy. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of doxorubicin. Vitamin E (200 IU/kg/week), catechin (200 mg/kg/week), doxorubicin (5 mg/kg/week), doxorubicin+vitamin E (200 IU/kg/week), doxorubicin+catechin (200 mg/kg/week) combinations were given to rats weighing 210-230g (n=6/group). Changes in major enzymes participating in free radical metabolism superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSHPx), catalase (CAT) and malondialdehyde (MDA) were evaluated in the livers of all animals. Superoxide dismutase and catalase activity increased in the doxorubicin-treated group compared to control (P < 0.05). Glutathione peroxidase levels increased in the catechin +doxorubicin-treated group (P < 0.05) and reached maximum concentrations in the doxorubicin-treated group compared to control (P < 0.01). Malondialdehyde levels increased in the doxorubicin-treated group compared to control and all-treated groups (P < 0.05). Malondialdehyde, glutathione peroxidase and catalase activities were decreased in the vitamin E+doxorubicin- and catechin+doxorubicin-treated group compared to doxorubicin-treated group (P < 0.05). All enzymes activities showed no statistical differences in the not mentioned groups above (P > 0.05). Electron microscopic studies supported biochemical findings. We conclude that vitamin E and catechin significantly reduce doxorubicin-induced hepatotoxicity in rats. (C) 2004 Elsevier Ireland Ltd. All rights reserved.