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

Oxidative stress is associated with alterations in arachidonic acid (AA) me tabolism. The present work was performed to assess the effect of the oxidan t tert-butyl hydroperoxide on the release of AA from rat hepatocytes, and t he possible preventive actions of estrogens on this effect. The exposure of [C-14]-prelabeled cells to tert-butyl hydroperoxide produced the mobilizat ion of [C-14]-AA from hepatocyte lipids, both an intracellular [C-14]-AA ac cumulation and an increased release of [C-14]-products into the medium bein g observed. The formation of lysophospholipids was also enhanced significan tly in the presence of the oxidant, thus suggesting the involvement of phos pholipase A(2) (E.C. 3.3.1.4) in the hepatocyte response to tert-butyl hydr operoxide. Estradiol and 2-hydroxyestradiol (25-100 mu M) added in vitro to cell suspensions prevented significantly the oxidant- mediated stimulation of AA release, this effect probably being caused by the estrogen inhibitor y actions against cellular lipid peroxidation.