title: Induction of NAD(P)H quinone oxidoreductase and glutathione S-transferase activities in livers of female August-Copenhagen Irish rats treated chronically with estradiol: comparison with the Sprague-Dawley rat.
abstract: Estradiol (E2) has been linked to both, protection against damage associated with chronic diseases or exposure to chemicals, and to the incidence of cancer. In its protective role, E2 appears to attenuate oxidative stress while as a carcinogen, E2 damages macromolecules via formation of reactive catechol metabolites. Alterations in the expression of antioxidant and xenobiotic metabolizing enzymes upon administration of pharmacological doses of E2 have been previously identified, but the effect of chronic exposure to low concentrations of E2 on activities of those enzymes in liver is unclear. The August-Copenhagen Irish (ACI) rat is more sensitive to estrogen-induced carcinogenesis than the Sprague-Dawley rat. Accordingly, the effect of treatment of female ACI and Sprague-Dawley rats for 6 weeks with E2 on activities of NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase, glutathione S-transferase (GST), phenol sulfotransferase (SULT1A1), cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) was studied. Basal expression of these enzymes was similar in livers from both strains prior to exposure to E2. However, only NQO1 and GST activity was increased (3- and 2.5-fold, respectively) in liver cytosol of ACI rats treated with E2. In contrast, only NQO1 activity was increased modestly in livers of Sprague-Dawley rats. Other enzymes were not significantly affected in the livers of ACI or Sprague-Dawley rats following chronic treatment with E2. The selective induction of NQO1 and GST activity suggests that under physiological conditions, E2 may protect against oxidative stress via elevation of these antioxidant enzymes. The marked induction of NQO1 and GST in the ACI rat indicates a potential for this strain to be used as a model to study the E2-mediated modulation of these enzymes in tissues that are either sensitive to E2 carcinogenesis or to its protective effects.
authors.affiliation: Laboratory for Cellular and Biochemical Toxicology, College of Pharmacy, Rutgers, The State University of New Jersey, 41 Gordon Road, Piscataway, NJ 08854, USA. rosa_sanchez@merck.com
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Sanchez
authors.forename: Sonia
authors.initials: S
authors.lastname: Mesia-Vela
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Kauffman
mesh_terms: D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D020719:Glucuronides / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000378:metabolism; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D011808:Quinone Reductases / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D020719:Glucuronides; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D005979:Glutathione Peroxidase; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase; D015239:Arylsulfotransferase