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 (E(2)). ACI rats were selected for study because this strain is highly responsive to treatment with low doses of E(2) as indexed by a high incidence of E(2)-induced mammary tumors compared to other strains. Rats were exposed chronically to 3 mg E(2) 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 E(2) 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 E(2) treatment. NQO1 was primarily localized in vascular elements and neurons and SULT1A1 primarily in neurons and neuropil of control and E(2)-treated rats. Collectively, these results suggest that enhanced expression of NQO1, GST, and SULT1A1 may contribute to the antioxidant effects of E(2) in the striatum, an area of the brain that may be particularly prone to oxidative stress because of its high content of catecholamines.
Stakhiv
Timothy M
TM
Laboratory for Cellular and Biochemical Toxicology, Joint Graduate Program of Toxicology, Rutgers, The State University of New Jersey and The University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Mesia-Vela
Sonia
S
Kauffman
Frederick C
FC
D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D011912:Rats, Inbred ACI; D012737:Sex Factors
D004958:Estradiol; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015239:Arylsulfotransferase