Phase II antioxidant enzyme activities in brain of male and female ACI rats treated chronically with estradiol

Activities of Phase II antioxidant enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UGT), and phenol sulfotransferase 1A1 (SULT1A1) were measured in brain of August–Copenhagen Irish (ACI) rats exposed chronically to low doses of estradiol (E2). ACI rats were selected for study because this strain is highly responsive to treatment with low doses of E2 as indexed by a high incidence of E2-induced mammary tumors compared to other strains. Rats were exposed chronically to 3 mg E2 contained in cholesterol pellets implanted subcutaneously for 6 weeks. This treatment increased activities of all four enzymes in the striatum of male but not female ACI rats. Blood E2 levels at time of sacrifice correlated closely with activities of striatal NQO1, GST, and SULT1A1, but not with striatal UGT. NQO1, GST, and SULT1A1 activities in other brain regions including the cortex, cerebellum, and hippocampus were less sensitive to chronic E2 treatment. NQO1 was primarily localized in vascular elements and neurons and SULT1A1 primarily in neurons and neuropil of control and E2-treated rats. Collectively, these results suggest that enhanced expression of NQO1, GST, and SULT1A1 may contribute to the antioxidant effects of E2 in the striatum, an area of the brain that may be particularly prone to oxidative stress because of its high content of catecholamines.