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 (E 2) 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, E 2 appears to attenuate oxidative stress while as a carcinogen, E 2 damages macromolecules via formation of reactive catechol metabolites. Alterations in the expression of antioxidant and xenobiotic metabolizing enzymes upon administration of pharmacological doses of E 2 have been previously identified, but the effect of chronic exposure to low concentrations of E 2 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 E 2 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 E 2. However, only NQO1 and GST activity was increased (3- and 2.5-fold, respectively) in liver cytosol of ACI rats treated with E 2. 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 E 2. The selective induction of NQO1 and GST activity suggests that under physiological conditions, E 2 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 E 2-mediated modulation of these enzymes in tissues that are either sensitive to E 2 carcinogenesis or to its protective effects.