Oxidative stress contributes to the pathogenesis of diabetes mellitus and its sequelae nephropathy. The kidneys are especially prone to damage by free radicals. We therefore tested the effect of the flavonoid mixture silymarin, a free radical scavenger, on the activity and gene expression of superoxide dismutase, glutathione peroxidase and catalase, as well as on renal tissue morphology in rats with alloxan-induced diabetes mellitus. Alloxan-intoxicated rats were treated with silymarin 20 days after alloxan administration for 9 weeks. Alloxan-induced tissue damage and decreased the activity of the three enzymes, SOD (U/mg prot.): 14.4 +/- 1.75 vs 112 +/- 6.45 control, p < 0.05, n = 6; GSHPx (mu M NADPH/min/mg prot.): 0.02 +/- 0.002 vs 0.121 +/- 0.01 control, p < 0.05, n = 6; CAT (k/seg/mg prot.): 0.022 +/- 0.003 vs 0.044 +/- 0.002 control, p < 0.05. n = 6. Silymarin treatment prevented tissue damage and restored the activity (SOD: 110.7 +/- 12.9 U/mg prot.; GSHPx: 0.329 +/- 0.031 mu M NADPH/min/mg prot.; CAT: 0.054 +/- 0.002 k/seg/mg prot., n = 6) and gene expression of the three antioxidant enzymes after 20 days of alloxan administration (SOD: 12.00 +/- 0.57 control, 9.00 +/- 0.1 diabetic p < 0.05, 11.00 +/- 0.20 silymarin treated; GSHPx: 6.01 +/- 0.78 control, 9.03 +/- 0.3 diabetic p < 0.05, 7.02 +/- 0.07 silymarin treated; CAT: 9.03 +/- 1.07 control, 12.02 +/- 0.60 diabetic p < 0.05, 8.06 +/- 0.31 silymarin treated, n = 6). It is suggested in this study that recuperative effect of silymarin on the renal tissue damage induced by alloxan may be related to an increase in the activity and recovery of gene expression of antioxidant enzymes which in addition to the glutathione system constitute some of the most important defense mechanisms against free radicals damage. As these results show, silymarin may be considered potentially in the treatment of diabetic nephropathy. (C) 2010 Elsevier GmbH. All rights reserved.