Inhibition by estrogens of the oxidant-mediated mobilization of arachidonic acid in hepatocytes

Oxidative stress is associated with alterations in arachidonic acid (AA) metabolism. The present work was performed to assess the effect of the oxidant tert-butyl hydroperoxide on the release of AA from rat hepatocytes, and the possible preventive actions of estrogens on this effect. The exposure of [14C]-prelabeled cells to tertbutyl hydroperoxide produced the mobilization of [14C]-AA from hepatocyte lipids, both an intracellular [14C]-AA accumulation and an increased release of [14C]-products into the medium being observed. The formation of lysophospholipids was also enhanced significantly in the presence of the oxidant, thus suggesting the involvement of phospholipase A2 (E.C. 3.1.1.4) in the hepatocyte response to tert-butyl hydroperoxide. Estradiol and 2-hydroxyestradiol (25-100 microM) added in vitro to cell suspensions prevented significantly the oxidant- mediated stimulation of AA release, this effect probably being caused by the estrogen inhibitory actions against cellular lipid peroxidation.