Hepatoprotective effects of equol through antioxidative and anti‐apoptotic function in 7,12‐Dimetylbenz(a)anthracene‐induced oxidative stress of mice

Abstract

We investigated the hepatoprotective effects of equol, the major metabolite of the antioxidant phytochemical daidzein, in mice with 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced oxidative stress. Oral pre‐administration of equol to mice who received DMBA intragastrically twice a week for 2 weeks significantly decreased their levels of biomarkers (thiobarbituric acid‐reactive substances, carbonyl content, and serum 8‐hydroxy‐2‐deoxyguanosine) of DMBA‐induced oxidative stress. Although several antioxidant enzymes were down‐regulated in DMBA alone treated mice, pre‐administration of equol blocked much of this effect, increasing catalase and superoxide dismutase activity in a dose‐dependent manner. Although equol did not affect the ratio of oxidized to reduced glutathione, it activated the glutathione peroxidase and glutathione reductase enzymes, and this effect was significant at a dose of 25 mg equol/kg body weight. DMBA treatment induced apoptosis, as shown by a decrease in the Bcl‐2 level and an increase in the levels of Bax, cleaved caspase‐3, and poly(ADP‐ribose) polymerase. These apoptotic effects were also reversed by equol at all doses tested. These results suggest that equol exerts a protective effect on mice with DMBA‐induced oxidative stress by acting as an antioxidant and by reducing apoptosis.