Characterization of the neuroprotective effects of estrogens on hydrogen peroxide-induced cell death in hippocampal HT22 cells: time and dose-dependency

Time and dose-dependency of the effects of estrogens (17-beta estradiol, es trone) and non-estrogenic steroids (progesterone, dexamethasone and methylp rednisolone) on the toxicity of hydrogen peroxide were examined in mouse hi ppocampal HT22 cells. Hydrogen peroxide, an important intermediate of various disease-relevant ox idative stressors, induced cell death in HT22 cells in extracellular concen trations between 0.5 and 1.5 mM in a dose-dependent manner (EC50=0.95 mM). Regarding the underlying mechanisms of toxicity incubation with hydrogen pe roxide did not induce lipid peroxidation in living HT22 cells under these c onditions. After preincubation with estrogens and non-estrogenic steroids f or 22 hours, estrogen compounds protected the cells against hydrogen peroxi de toxicity. Estrogens showed a maximal protective effect at 60-70% of hydr ogen peroxide toxicity which diminished at higher and lower concentrations of the toxic challenge. Dose-dependency studies of estrogens revealed that concentrations of 1 mu M already exerted a significant cytoprotective effec t. Co- and postincubation with 17-beta estradiol and estrone also resulted in significant cell protection even if the estrogens were added 30 min afte r the initiation of the challenge with hydrogen peroxide. In contrast, preincubation with other steroids like progesterone. a physiol ogical gonadal steroid, dexamethasone, a synthetic glucocorticoid and methy lprednisolone, a glucocorticoid with radical scavenging properties, did not protect the cells against hydrogen peroxide toxicity but resulted in a dos e-related decrease of HT22 cell survival in the course of the toxic challen ge.