Chronic equol administration attenuates the antioxidant defense system and causes apoptosis in the mouse brain

We investigated the effects of equol on the antioxidant defense system and apoptosis in the brains of mice administered equol at 5 or 25 mg/kg BW for 3 or 7 weeks. The effects of equol on the antioxidant defense system differed with the administration conditions. At 3 weeks, equol significantly inhibited lipid peroxidation and increased the catalase and total SOD activity in a dose-dependent manner, although equol did not have much effect on the GSH-related system. Following equol administration for 7 weeks, the level of TBARS was increased, while the catalase and total SOD activity were attenuated, although the difference was significant only at the higher dose. Moreover, at the higher dose, equol significantly downregulated the GSH-related defense system. The GSH/GSSG ratio was decreased in a dose-dependent manner, as was the GSH-px and GR activity. As a result of these changes, apoptosis was induced in the mouse brain at both doses. The apoptosis process in the brain triggered by equol at the higher dose was consistent with a report that equol leads to apoptosis via p53 activation in vitro. Based on our results, chronic equol administration at a higher dose may disrupt the antioxidant defense system and induce apoptosis in the mouse brain.