Hepatoprotective effects of daidzein against 7,12-dimetylbenz[a]anthracene-induced oxidative stress in mice

We investigated the effects of daidzein on the antioxidant defence system in mice with 7,12-dimethylbenz[a]-anthracene (DMBA)-induced oxidative stress. Daidzein was administered orally at 5 and 25 mg/kg body weight for 5 weeks. Subsequently, mice pretreated with daidzein received DMBA intragastrically twice a week for 2 weeks. As controls, mice were given vehicle or DMBA alone. In the DMBA group, biomarkers of oxidative stress (thiobarbituric acid reactive substances value, carbonyl content) were significantly increased. However, the rise in oxidative damage was significantly reduced by daidzein at the higher dose. In addition, several antioxidant enzymes were downregulated in the DMBA-treated mice. Catalase and superoxide dismutase activity was increased by daidzein in a dose-dependent manner. Although the reduced/oxidized glutathione ratio was unaffected, glutathione peroxidase and reductase were activated by daidzein, and the effect was significant at the higher dose. Further, in the DMBA-treated mice, apoptosis was induced by a decrease in Bcl-2 and an increase in Bax. These changes were restored to their normal values in the daidzein-treated mice. Upregulation of caspase-3 was also decreased by daidzein. These results suggest that daidzein exerts a hepatoprotective effect on mice with DMBA-induced oxidative stress through its antioxidant activity and the reduction of apoptosis.