The clinical use of doxorubicin (Dxr), an antineoplastic agent, is limited by its extensive toxicity which is mostly mediated by oxidant injury. We have studied the effect of erdosteine. a mucolytic drug showing antioxidant properties, in preventing Dxr-toxicity to improve future Dxr therapy. Male Sprague-Dawley rats were divided into four groups. The first group that underwent no medication was accepted as control groups the second group was treated with a single i.p. injection of Dxr (20 mg kg(-1) bwt.); the third group was treated with oral erdosteine alone (10 mg kg(-1) b.wt. day(-1) for 12 days): and in the last group erdosteine was administered starting before Dxr injection for 12 days. The thiobarbituric acid reactive substances (TBARS) level of Dxr group was higher in both plasma and erythrocyte than the other groups. In plasma and erythrocyte. the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were increased in Dxr plus erdosteine group in comparison with control group, and the activities of GSH-Px were increased in Dxr plus erdosteine group in comparison with Dxr group. The erythrocyte catalase (CAT) activity of Dxr plus erdosteine group was higher than control and Dxr groups. Plasma xanthine oxidase activities and nitric oxide (NO) levels were not significantly different between groups. however erythrocyte NO level of Dxr group was higher than control, In conclusion. Dxr administration resulted in increased lipid peroxidation in plasma as well as erythrocyte and erdosteine treatment helped to prevent oxidative injury by increasing antioxidant enzymes, especially SOD. GSH-Px and CAT, in rats. (C) 2003 Elsevier Science Ltd. All rights reserved.